Tuesday, May 29, 2012

Academic effects of contact sports on college athletes

Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes

While it is known that concussions can harm an athlete’s ability to learn, a new study has found evidence that even one season of contact sports can affect how well some athletes acquire new information, according to the study’s lead author and Director of Neuropsychiatry at the Geisel School of Medicine Thomas McAllister.

The research was part of a multi-institution study that has been working for five or six years to understand the biomechanical basis and effects for concussions, McAllister said.
The study, which was published by the American Academy of Neurology, found that contact sport athletes did not perform worse than non-contact sports athletes on cognitive tests before their seasons began. These results were “reassuring,” McAllister said.

“We did not find any systematic widespread adverse affects on cognition,” he said. “The two groups on average looked pretty similar at the end of the season.”

The study did find that a larger subgroup of contact sport athletes than non-contact sports athletes performed worse than expected on tests taken immediately after the season. Taking into account how well the athletes tested before their season began and controlling for other indicators of general test performance and the interval between tests, the authors predicted how well the athletes should perform after their season and compared this to their actual results.

“We found that about 22 percent [of contact sport athletes] did worse than 1.5 standard deviations below what we would have predicted,” McAllister said. “This was a significant difference from the non-contact group.”

McAllister said that this raises the possibility that some individuals are particularly vulnerable to suffering negative effects from hitting their heads repeatedly during contact sports.
“This changes the emphasis of the debate a little bit,” McAllister said. “It’s a new direction for us to be thinking about the risks or lack of risks for contact sports. There may not be the same risk for everyone.”

The researchers also used the tests administered at the beginning of the season to see whether athletes who had been playing contact sports for most of their lives and had presumably hit their head more often had lower cognition than non-contact sport athletes.
“We did not find any systematic differences between the two athlete groups at the beginning of the season,” McAllister said. “We think this is good news. We were unable to detect widespread significant differences in their cognitive capabilities.”

To measure their results, researchers administered two tests to male and female contact and non-contact sport athletes from the College, Brown University and Virginia Polytechnic Institute and State University at the beginning and end of their seasons. Contact sport athletes played football or ice hockey while non-contact sport athletes participated in track, Nordic skiing or crew.

Participants that sustained a documented concussion during the season were not included in the study results because researchers were primarily interested in the effects of “repetitive impacts to the head not apparently causing a concussion,” according to McAllister.
A 20-minute computerized test measured cognition, memory attention and reaction time. The other neurological test, administered to a sub-group of athletes, was more extensive and used “paper and pencil.” Researchers compared the results of the contact sport athletes’ tests with the non-contact sport athletes’ tests, which were used as a control.
Contact sport athletes wore special helmets during practice and games equipped with a Head Impact Telemetry System designed by Richard Greenwald, the president of Simbex, a technology company in Lebanon. The helmets have been in use since 2004 around the United States, according to Greenwald.

“The helmets contain a system that monitors head impacts automatically and wirelessly,” Greenwald said. “They measure how often, how hard and where on the helmet gets hit.”
Jessica Gagner ’13 plays women’s ice hockey and participated in the study as a contact sport athlete. She said she was not more cognizant about hitting her head when wearing the helmet.

“To me, if you’re playing a contact sport, you’re obviously going have a bigger effect on your head,” Gagner said. “It’s really inevitable that you’re going to have more of an issue with head impacts if you are a contact sport athlete.”
Cara Vernacchia ’13 runs track and was a non-contact athlete who participated in the study. She said she was glad to be able to take part to help researchers learn more about concussions and how to prevent them.

“Being able to be part of the study made me realize that concussions do occur,” Vernacchia said. “It’s interesting to see how prominent head impacts are, even on our campus.”
The researchers hope to continue observing the effects of contact sports on the study’s participants. Many students agreed to undergo neuroimaging before and after their seasons and researchers hope to examine these results.

“We’d love to be able to revisit with some of these athletes four or five years down line and get a second set of test results to see how they’re doing after a whole collegiate career,” McAllister said.

The researchers also hope to learn more about why certain athletes performed worse than expected on tests after a season of contact sports.
“I think the second theme of ongoing research would be to try and understand what individuals are at risk to be in that ‘not doing as well as we would have thought’ category,” McAllister said.

Greenwald said that the researchers hope to learn more about the effects of contact sports on youth and women in the future.

Read more here:

Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes

  1. J.H. Turco, MD
+Author Affiliations
  1. From the Departments of Psychiatry (T.W.M., L.A.F., A.M., M.R.G.), Community and Family Medicine (T.D.T.), and Medicine (J.H.T.), Dartmouth Medical School, Lebanon; Simbex (R.M.G., J.G.B.), Lebanon; Thayer School of Engineering (R.M.G.), Dartmouth College, Hanover, NH; Bioengineering Laboratory, Department of Orthopaedics (J.J.C.), The Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, RI; Edward Via Virginia College of Osteopathic Medicine (P.G.B.), Blacksburg; Virginia Tech-Wake Forest (S.M.D.), Center for Injury Biomechanics, Blacksburg; Pediatric Neurosurgery (A.-C.D.), Children's Hospital at Dartmouth, Dartmouth Hitchcock Medical Center, Hanover, NH; and Pediatric Neurosurgery (A.-C.D.), Massachusetts General Hospital, Boston.
  1. Correspondence & reprint requests to Dr. McAllister: thomas.w.mcallister@dartmouth.edu


Objective: To determine whether exposure to repetitive head impacts over a single season negatively affects cognitive performance in collegiate contact sport athletes.
Methods: This is a prospective cohort study at 3 Division I National Collegiate Athletic Association athletic programs. Participants were 214 Division I college varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration-time history of the head following impact, and 45 noncontact sport athletes. All athletes were assessed prior to and shortly after the season with a cognitive screening battery (ImPACT) and a subgroup of athletes also were assessed with 7 measures from a neuropsychological test battery.
Results: Few cognitive differences were found between the athlete groups at the preseason or postseason assessments. However, a higher percentage of the contact sport athletes performed more poorly than predicted postseason on a measure of new learning (California Verbal Learning Test) compared to the noncontact athletes (24% vs 3.6%; p < 0.006). On 2 postseason cognitive measures (ImPACT Reaction Time and Trails 4/B), poorer performance was significantly associated with higher scores on several head impact exposure metrics.
Conclusion: Repetitive head impacts over the course of a single season may negatively impact learning in some collegiate athletes. Further work is needed to assess whether such effects are short term or persistent.

What to know about seizures - A Primer - Basic information for your acquaintances or a concerned neighbor

Editor's Note: This is very basic information for your acquaintances or the concerned neighbor.

Darla Templeton, CEO of Epilepsy Foundation of Missouri and Kansas, said the 40 different types of epilepsy, or seizure disorder, exhibit various physical displays, so reactions vary when a seizure occurs. However, they all come down to keeping the person safe and judging whether it is a medical emergency requiring assistance.

"The most important thing about any of them is that you shouldn’t put something in a person’s mouth. That was the procedure suggested long ago, but it was found that people broke their teeth and it didn’t work well," she said.

Three situations require calling 911:

  • A seizure lasting more than five minutes, 
  • if it immediately reoccurs or 
  • when it is the first one.

As a seizure passes, the person experiencing it will be slightly confused, so an onlooker should be reassuring and calm. Once senses clear to provide correct information like name and location, he probably can continue.

While a person with epilepsy certainly can enjoy summer, Templeton said, it is imperative always to swim with a buddy. If someone has a seizure while swimming, onlookers should get him out of the water for seizure control, plus check for possible water ingestion.

Generalized tonic clonis (grand mal)

Symptoms: Loss of consciousness, muscles stiffen and jerk, usually lasts 2 to 3 minutes.

What to know:
  • Ease him to the ground if he already hasn’t fallen.
  • Protect the head and remove things around him for safety.
  • Turn him on his side. Loosen a collar, if wearing one.

Complex partial seizure

Symptoms: Impaired awareness, pulls on clothes, lip movement, aimless walking, usually shorter duration.

What to know:

  • Try to keep out of harm’s way, particularly if person is walking.
  • May be misinterpreted as other ailment like drug abuse or drunkenness.
  • Holding or steering the person for safety may be misunderstood and push away the aid.

Absence seizure (petit mal)

Symptoms: Eyes roll back, flutter or stare for a few seconds.

What to know: Awareness returns just after a short period of unresponsiveness.

Read more: HERE

Study Claims Fever During Pregnancy More Than Doubles the Risk ofAutism or Developmental Delay

Editor's Note: Parent guilt is a very heavy burden. I am happy to see another study that might help to ease that load. How can you prevent getting a fever?

A team of UC Davis researchers has found that mothers who had fevers during their pregnancies were more than twice as likely to have a child with autism or developmental delay than were mothers of typically developing children, and that taking medication to treat fever countered its effect.

"Our study provides strong evidence that controlling fevers while pregnant may be effective in modifying the risk of having a child with autism or developmental delay," said Ousseny Zerbo, lead author of the study, who was a Ph.D. candidate with UC Davis when the study was conducted and is now a postdoctoral researcher with the Kaiser Permanente Northern California Division of Research. "We recommend that pregnant women who develop fever take anti-pyretic medications and seek medical attention if their fever persists."

Published online in the Journal of Autism and Developmental Disorders, the study is believed to be the first to consider how fever from any cause, including the flu, and its treatment during pregnancy could affect the likelihood of having a child with autism or developmental delay.
The results are based on data from a large, case-control investigation known as the Childhood Autism Risk from Genetics and the Environment (CHARGE) Study. Another recent study based on CHARGE data found that mothers who were obese or diabetic had a higher likelihood of having children with autism.

Irva Hertz-Picciotto, a professor of public health sciences at UC Davis and principal investigator of CHARGE, pointed out that fever is produced by acute inflammation -- the short-term, natural immune system reaction to infection or injury -- and that chronic inflammation, which no longer serves a beneficial purpose and can damage healthy tissue, may be present in mothers with metabolic abnormalities like diabetes and obesity.

"Since an inflammatory state in the body accompanies obesity and diabetes as well as fever," said Hertz-Picciotto, "the natural question is: Could inflammatory factors play a role in autism?"
She explained that when people are infected by bacteria or viruses, the body generally reacts by mounting a healing response that involves the release of pro-inflammatory cytokines from white blood cells into the bloodstream. Some cytokines are able to cross the placenta, and therefore could reach the fetal central nervous system, potentially altering levels of neurotransmitters and brain development.

"We definitely think more research is necessary to pinpoint the ways that inflammation could alter brain development," said Hertz-Picciotto.

Read more here: http://www.sciencedaily.com/releases/2012/05/120523161941.htm

Study: CPAP treatment was tied to lowered odds for high blood pressure

New research suggests that treating obstructive sleep apnea, a common cause of snoring and daytime sleepiness, might also cut down on a serious health hazard associated with the condition -- the risk of developing high blood pressure.

Researchers in Spain examined the number of new cases of high blood pressure in two groups with sleep apnea who used continuous positive airway pressure therapy, or CPAP, for either about four or 11 years. CPAP involves the use of a mask to help push air into the lungs while asleep.

The results were published in a pair of studies in the May 23/30 issue of the Journal of the American Medical Association.

Both studies found that people who used CPAP, the most common treatment for sleep apnea, for at least four hours a night had lower rates of developing high blood pressure compared with those who were not prescribed CPAP or who used it less regularly.

"CPAP seems to have a protective effect in patients who use the machine properly," said Dr. José Marin, director of the Sleep Respiratory Unit at Miguel Servet University Hospital in Zaragoza, an author of both studies.

However, about 10 percent of people used the machine for fewer than four hours nightly, which is considered the minimum amount to see benefits, Marin said.

Many patients are uncomfortable with CPAP because it is inconvenient and the mask covers their nose while they sleep, or the person they sleep with does not like the noise the machine makes, Marin said.

But alternative treatments, such as surgery or mouth devices, generally don't work as well as CPAP, and there are less data suggesting they reduce the risk of high blood pressure, said Dr. Aneesa Das, assistant director of the sleep disorders program at the Ohio State University Wexner Medical Center.

A reduction in high blood pressure risk could also reduce the risk of other diseases, such as heart failure, which are more common in people with sleep apnea. "The idea is that there are probably multiple factors that are causing cardiovascular events and stroke [in sleep apnea patients], including [high blood pressure]," said Das.

It is estimated that 17 percent of U.S. adults have obstructive sleep apnea, which occurs when the airway closes during sleep and restricts breathing. It can cause people to wake up repeatedly and can lead to low levels of oxygen in the blood.

One of the studies included about 1,900 patients at Marin's sleep clinic who did not have high blood pressure. Their average age was 50.

The researchers assigned participants to CPAP treatment if they had severe obstructive sleep apnea or a less severe form along with daytime sleepiness. Then they measured their blood pressure each year for an average of 11 years.

The investigators found that patients with sleep apnea who used CPAP therapy were 29 percent less likely to develop high blood pressure during the study than the "control" group, which did not have sleep apnea and did not receive CPAP. However, as Marin pointed out, the people in the control group were "snorers, and they have been reported to have cardiovascular problems."

The researchers also found that patients with sleep apnea who did not use CPAP had higher rates of high blood pressure compared with the control group.

For example, the 10 percent of 922 participants who did not use CPAP at least four hours a night had a 78 percent higher risk of developing high blood pressure than the control group.

The researchers found that the lower risk of high blood pressure in the CPAP group could not be explained by differences in factors such as patients' body mass index (a measurement that takes into account height and weight), alcohol use or blood pressure at the beginning of the study.

However, there could still be differences between the CPAP-treated and untreated groups that could make the CPAP group less likely to develop high blood pressure, Marin said.

Marin and his colleagues conducted a second study in which they randomly assigned 725 patients who had obstructive sleep apnea but not daytime sleepiness to use CPAP or not to use CPAP. Then they tracked participants' blood pressure and heart disease for an average of four years.

At first the researchers did not see a statistically significant difference between the groups. However, 36 percent of the CPAP group was using the machine less than four hours a night.

In a follow-up analysis, which the authors pointed out may be open to bias, the researchers found that patients using CPAP for at least four hours a night were 28 percent less likely than the control group to develop high blood pressure.

Dr. Stuart Quan, professor of sleep medicine at Harvard Medical School in Boston, wasn't surprised by the findings. "I already believe that sleep apnea impacts [high blood pressure] and treating with CPAP reduces the risk, so these studies do not affect my way of thinking about this," he said.

Quan added that he prescribes CPAP to patients with at least moderate obstructive sleep apnea or those with sleep apnea and symptoms such as daytime sleepiness or mood problems.

Medicare requires patients to use CPAP at least four hours a night for 70 percent of nights to cover the treatment. The insurance deductible for CPAP is usually between $100 and $500, Quan said.

While the study uncovered an association between CPAP use and reduced risk of developing high blood pressure, it did not prove a cause-and-effect relationship.

Read more here: http://www.nlm.nih.gov/medlineplus/news/fullstory_125454.html

The difference between ADD and ADHD

Dennis the Menace may be the most beloved ADHD cartoon character ever! Impulsive and hyperactive, he makes the afflicted Dory, the ever-swimming, easily distracted Regal Blue Tang from "Finding Nemo," look focused. Turns out that attention deficit hyperactivity disorder (ADHD) -- an all-inclusive term that swallowed up attention deficit disorder (ADD) -- comprises a cluster of symptoms from mildly inattentive to disruptively agitated and shows up differently in boys and girls.

ADHD contains three subtypes of behavior: 1) hyperactive-impulsive; 2) inattentive (what was formerly ADD); and 3) hyperactive-impulsive and inattentive combined. A child can have any combination or degree of these behaviors.

One theory that explains why more boys (13 percent) are diagnosed than girls (6 percent) is that girls tend to be less disruptive, more daydreamy and have attention deficit; while boys are hyperactive-impulsive. They're the squeaky wheel!

For all kids, diagnosis requires repeatedly inappropriate behavior and/or chronic inattention and clear differences between a child's behavior and capabilities and those of his or her peers. Adults diagnosed with ADHD must have had their symptoms since childhood.

Both kids and adults are treated with medication and psychotherapy. Treatment protects kids (and adults) from developing antisocial behaviors, addictions, anxiety and eating disorders, particularly binge-eating and obesity.

So, if you (or someone you love) have trouble making friends, holding a job, paying attention or controlling impulses, opt for diagnosis and treatment. It might provide a huge improvement in daily life. And helping yourself, a friend or family member get healthier always makes your RealAge younger.

Read more here: http://www.herald-dispatch.com/news/x1190167523/ADHD-vs-ADD-Whats-the-difference

Diet may lead to epilepsy drugs

A fatty diet that helps control epileptic seizures may do so by triggering a chemical change in the brain, a discovery that could lead to new treatments, according to a Harvard University study.
The diet may force a protein to switch the brain’s fuel to fat byproducts called ketones from its preferred energy, glucose, according to a study in genetically manipulated mice in the journal Neuron. Making the brain operate on ketones is known to shut down overexcited neurons that cause seizures.
This so-called ketogenic diet is used by epilepsy patients who aren’t helped by seizure-reducing drugs. The patients are only allowed a saltine cracker’s worth of carbohydrates daily, said Gary Yellen, a study author. That’s hard to do, and new treatments based on the diet’s effects in the body may lead to better control of seizures, he said.
“There are kids who go off this diet because they and their parents can’t manage it,” said Yellen, a professor of neurobiology at Harvard Medical School in Boston. “Having a pharmaceutical to help them would be important.”
Epilepsy is a brain disorder that causes repeated seizures, where neurons fire in a disorganized and sudden way, according to the National Institutes of Health. About 3 million Americans are epileptic, according to the Landover, Maryland-based Epilepsy Foundation, an advocacy group.
Mimicking the Protein
Yellen’s coauthor, Nika Danial, an assistant professor of cell biology at the Dana-Farber Cancer Institute, is working on mimicking the protein. That may lead to a treatment, or help researchers look through chemical libraries for something similar, she said.
The diet is very high in fat, with some protein and almost no carbohydrates, triggering the body to use fat as its source of energy and imitating the effects of starvation on the body. That releases ketones, which can provide energy to the brain in lieu of sugar.
In epileptic mice, the scientists tinkered with a protein called BCL-2-associated agonist of cell death, or BAD, to promote ketones and lower levels of glucose. While their seizures decreased, there was no effect in mice that had been genetically altered to take out the protein, providing evidence for how it worked, according to the study.
The switch is much like changing from diesel to unleaded fuel, causing fewer seizures, Yellen said. Something about the swap prevents neurons from firing too much, though the full extent of the changes isn’t clear. Additionally, a ketogenic diet may be effective in some neurodegenerative disorders, Danial said.
“This could have broader implications for the protective effects of being able to reprogram what the brain burns,” Danial said.
The study was funded by Harvard Catalyst, Citizens United for Research in Epilepsy, and the NIH.

Autism usually not diagnosed until age 5 or older

Editors' note: Early diagnosis and  intervention can modify outcome. If you are concerned, seek an evaluation by a pediatric neurologist, psychiatrist or developmentalist. JR

Even though autism symptoms typically emerge before age 3, most children with autism are diagnosed when they're 5 or older, a new snapshot of autism in America shows.

More than half of U.S. children with an autism spectrum disorder are taking at least one psychotropic medicine -- including stimulants, anti-anxiety medications, antidepressants, sleep aids, seizure medications or antipsychotics -- even though there are no drugs that have clearly been shown to impact the core symptoms of the disorder.

The findings are from a nationally representative survey of more than 4,000 parents or guardians of children with special needs aged 6 to 17, including about 1,400 who had an autism spectrum disorder. The report was compiled by researchers from the U.S National Institute of Mental Health in conjunction with the U.S. Centers for Disease Control and Prevention.

"This is a snapshot of what the nation looks like. American families can compare their experience to what others have found," said study co-author Lisa Colpe, chief of the office of clinical and population epidemiology research at the U.S. National Institute of Mental Health.

Among the other key findings:

About 19 percent of kids were diagnosed with an autism spectrum disorder at age 2 or younger; 17 percent were diagnosed at age 3; 13 percent were age 4; 11.5 percent were age 5; and nearly 40 percent were 6 or older when they were diagnosed.
Children were identified by a range of health care professionals, including pediatricians, family physicians, nurse practitioners, psychologists, developmental psychologists, neurologists and multidisciplinary teams.
Nine of 10 school-aged children with an autism spectrum disorder use at least one service to meet their developmental needs, while just over half of the kids use three or more services.
The most common service is social skills training, followed by speech or language therapy. Others include behavioral interventions and occupational therapy.
Geraldine Dawson, chief science officer for Autism Speaks, said findings show the continued need to work toward identifying children earlier.

"Research tells us that children who start intervention earlier do better in the long run. This report found that the majority of children were 5 years or older when they were first identified. We can reliably diagnose autism by 24 months, so professionals need to do a better job, including screening all children at 18 and 24 months," Dawson said.

Only about 40 percent of school-aged children with an autism spectrum disorder receive behavioral intervention, even though research has shown such strategies can "significantly improve outcomes," she added.

Lack of insurance coverage and too few trained providers with expertise in behavioral interventions are reasons why some children aren't getting the services, Dawson noted. "It is critical that we address the barriers that are preventing children from receiving early intervention. Early intervention will result in better outcomes for children and provide substantial cost savings in the long run," Dawson said.

Autism is a neurodevelopmental disorder characterized by problems with social interaction, communication and restricted interests and behaviors. That includes repetitive behaviors, such as arm-flapping or head-banging; having an obsessive interest in one topic; having a need to stick to a specific ritual or routine; and experiencing distress or agitation when that routine gets disrupted.

About one in 88 U.S. children has the disorder, according to the CDC.

Children with autism can also have co-existing conditions, such as anxiety, seizures, depression or attention-deficit/hyperactivity disorder (ADHD). Experts say it's not always easy for parents and doctors to know whether symptoms are autism-related or a co-existing condition, but many will try various drugs to alleviate the symptoms.

"The findings with respect to psychotropic medication use is in line with previous findings," Dawson said. "Children with autism often have co-occurring conditions, such as ADHD and anxiety, which are often helped with medication."

Because some of the drugs to treat those conditions can be powerful, Colpe said it was a good sign that so many children (upwards of 90 percent) were also receiving some other sort of treatment, indicating that they are being monitored by a physician.

"They are getting a multi-mode treatment," Colpe said.

Read more here: http://www.nlm.nih.gov/medlineplus/news/fullstory_125545.html

Monday, May 28, 2012

Down Syndrome Treatment Trial

Rivastigmine Study in Adolescents With Down Syndrome (DS Riv)
This study is currently recruiting participants.
Verified March 2012 by Duke University

First Received on March 8, 2010.   Last Updated on March 20, 2012   History of Changes
Sponsor:Duke University
Collaborator:Taishoff Family Foundation
Information provided by (Responsible Party):Duke University
ClinicalTrials.gov Identifier:NCT01084135
The purpose of this study is to determine if short term use of rivastigmine can improve functional abilities (for example, language, memory, and executive function) in adolescents with Down syndrome.

Down SyndromeDrug: Rivastigmine
Other: Liquid Placebo
Phase 1
Phase 2

Study Type:Interventional
Study Design:Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title:A 20-Week Double-Blind Placebo Controlled Clinical Trial to Evaluate the Safety and Efficacy of Rivastigmine in Children (Ages 10-18) With Down Syndrome

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) [ Time Frame: Baseline & Study termination (Week 20) ] [ Designated as safety issue: No ]
    Indirect (parent report) measure of adaptive function

Secondary Outcome Measures:
  • Behavior Rating Inventory of Executive Function-Preschool (Brief-P) [ Time Frame: Baseline and Final (Week 20) visit ] [ Designated as safety issue: No ]
    Indirect measure of executive function

Estimated Enrollment:40
Study Start Date:November 2009
Estimated Study Completion Date:May 2013
Estimated Primary Completion Date:February 2013 (Final data collection date for primary outcome measure)
ArmsAssigned Interventions
Experimental: Rivastigmine- Liquid form
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
Drug: Rivastigmine
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. Subjects receiving placebo will maintain the same schedule. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose,down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
Other Name: Rivastigmine-Excelon
Placebo Comparator: Liquid placebo
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Other: Liquid Placebo
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.

Detailed Description:
This 24 week, double-blind, placebo controlled trial will be completed at the Clinical Research Unit of Duke University Medical Center and at the Kennedy Krieger Institute (KKI). Sixteen evaluable subjects will be enrolled at Duke and 24 evaluable subjects will be enrolled at KKI. The study consists of four visits, a screening visit (-4 weeks), a baseline visit (week 0); a safety visit at week 10, and a final/termination visit at week 20.
The specific aims of this study are to: a) investigate efficacy of rivastigmine tartrate treatment; b) build upon our open-label treatment results of overall function and language improvement in adolescents with Down syndrome (DS) in a double-blind, placebo-controlled clinical trial; and c) investigate other specific cognitive domains that may selectively respond to rivastigmine tartrate treatment.

Ages Eligible for Study:  10 Years to 17 Years
Genders Eligible for Study:  Both
Accepts Healthy Volunteers:  No
Inclusion Criteria:
  1. Correct VERBAL responses for 7/9 of the Expressive One Word Picture Vocabulary Test items.
  2. Subject able to put at least 2-3 words together in conversational speech.
  3. Subject's speech is understandable to the examiner for the majority of the time.
  4. Subjects are in good health and medically stable
Exclusion Criteria:
  1. Subject uses sign language as a primary means of communication
  2. Subject has a medical history that contraindicate the use of rivastigmine (For example, patients with active seizure disorders, asthma, celiac disease, heart disease or heart rhythm disorders).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01084135

Contact: Jane Ann McKillop, MS, CGC919-668-4576janeann.mckillop@duke.edu
Contact: Blythe Crissman, MS, CGC919-681-1976criss004@mc.duke.edu

United States, Maryland
Kennedy Krieger InstituteRecruiting
Baltimore, Maryland, United States, 21205
Contact: Cathleen Weadon, BA     410-923-9140     weadon@kennedykrieger.org    
Principal Investigator: George Capone, MD            
Sponsors and Collaborators
Duke University
Taishoff Family Foundation
Principal Investigator:Priya Kishnani, MDDuke University
  More Information

No publications provided

Responsible Party:Duke University
ClinicalTrials.gov Identifier:NCT01084135     History of Changes
Other Study ID Numbers:Pro00013682
Study First Received:March 8, 2010
Last Updated:March 20, 2012
Health Authority:United States: Institutional Review Board

Keywords provided by Duke University:
Clinical trial
Down syndrome

Additional relevant MeSH terms:
Down Syndrome
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 24, 2012


RETT Syndrome TREATMENT Trial Recruiting

Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)
This study is currently recruiting participants.
Verified March 2012 by Children's Hospital Boston

First Received on December 2, 2010.   Last Updated on March 19, 2012   History of Changes
Sponsor:Scott Pomeroy
Collaborators:International Rett Syndrome Foundation
Autism Speaks
Information provided by (Responsible Party):Scott Pomeroy, Children's Hospital, Boston
ClinicalTrials.gov Identifier:NCT01253317
The investigators are recruiting children for a research study using a medication known as IGF-1 (mecasermin or INCRELEX) to see if it improves the health of children with Rett syndrome (RTT). To participate in the study your child must be female, between the ages of 2 to 12 and have a genetic diagnosis (MECP2 deletion or mutation) of Rett Syndrome. As you may know, there is no treatment for this illness. Currently, the standard management of Rett syndrome is supportive, which means attempting to prevent complications and treatment of symptoms.
This study involves testing an investigational drug, which means that even though IGF-1 is approved by the Food and Drug Administration (FDA) for use in children, it has not been used before to treat Rett syndrome specifically. Information from this research will help determine whether the drug should be approved by the FDA in the future for the treatment of Rett Syndrome.
There are five major goals to this study:
  1. As one of the features of Rett Syndrome is unstable vital signs, the investigators are trying to determine if IGF-1 has any effect on normalizing your child's pulse, blood pressure and breathing pattern. During PHASE 2, a device called BioRadio® will be used to monitor vital signs in a non-invasive way. This information will be recorded and stored on the accompanying laptop. Before starting PHASE 2, the investigators would like to "beta-test" the BioRadio® in PHASE 1. As such, the investigators may ask you to try using the BioRadio® with your child to test the fit and the performance of the equipment. Should you choose to enroll your child in PHASE 2, the investigators will then ask that your child wear the BioRadio® for two hours, on two consecutive days every four weeks.
  2. The safety of IGF-1 in children with Rett syndrome. The study personnel will ask you to complete a medication diary and side effect reporting form on a regular basis. They will assist you in completing this by telephone interviews. Your child will undergo 2 lumbar punctures performed at the bedside in the clinical research facility. In addition, laboratory tests will be performed throughout the study to evaluate the safety of IGF-1. These will be blood tests similar to those provided in routine clinical care. Your child will undergo regular non-invasive comprehensive physical examinations including neurological and eye examination, tonsil evaluation, electrocardiograms (ECG), measurement of height, weight and head circumference.
  3. IGF-1 may improve your child's behavior, communication and speech. In order to measure this, the investigators will evaluate your child once during each month of treatment with neurodevelopmental assessments and a neurological exam. All of the tests used during these evaluations are non-invasive. the investigators will also ask you what your impressions are about her behavior and day-to-day activities through a structured parental interview and various questionnaires.
  4. We will examine your child's cortical function through use of electroencephalography (EEG) in conjunction with presentation of visual and auditory stimuli. EEG is a non-invasive way of recording the electrical activity of your child's brain by applying a net of electrodes to her scalp. Through this we gain insight into how neural function correlates to the progression of behavioral abnormalities seen in individuals with RTT. By understanding how this electrical brain activity produces the abnormal behaviors seen in RTT, we will be better able to identify whether or not treatment with IGF-1 affects the way the brain communicates with the body.
  5. Children with Rett Syndrome are often unable to regulate their body temperature and will sometimes experience "flushing" in their cheeks or have exceptionally cold hands or feet. The Qsensor® is a non-invasive device worn on a fabric bracelet that continually measures your child's perspiration level and body temperature. We would like to use the Qsensor® to determine whether or not IGF-1 improves your child's ability to regulate her body temperature. As such, we ask that your child wear the Qsensor® during each study visit. This wrist-worn sensor has been demonstrated to be safe and comfortable but may cause a slight gray discoloration where the sensor contacts your child's skin. This discoloration will go away in less than a day. The Qsensor® is not waterproof, therefore may not be worn in the shower or while your child is washing her hands. If you believe the device is broken, please contact the study team immediately.

Rett SyndromeDrug: rhIGF-1Phase 1
Phase 2

Study Type:Interventional
Study Design:Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • respiratory inductance plethysmography [ Time Frame: every five weeks during each 20-week arm ] [ Designated as safety issue: No ]
    The primary outcome measure will be the index of autonomic/respiratory dysregulation, using non-invasive respiratory inductance plethysmography. The data for index calculation are derived from a device known as the BioRadio®. The BioRadio® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and 3 lead ECG signal.
  • Electrocardiogram [ Time Frame: every five weeks during each 20-week arm ] [ Designated as safety issue: No ]
    The BioRadio® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It will be configured for the pediatric chest with 3 lead ECG signals.

Secondary Outcome Measures:
  • Growth Measurements [ Time Frame: every five weeks throughout each 20-week arm ] [ Designated as safety issue: Yes ]
    measuring height, weight, head circumference
  • Clinical Assessment [ Time Frame: every five weeks during each 20-week arm ] [ Designated as safety issue: No ]
    assess severity of neurological and motor symptoms of Rett Syndrome.
  • Clinical Severity Scale [ Time Frame: every five weeks during each 20-week phase ] [ Designated as safety issue: No ]
    measures severity of clinical features of Rett Syndrome
  • Fundoscopic [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: Yes ]
    Assesses cranial pressure.
  • Tonsillar and Otolaryngological Exam [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: Yes ]
    Measures tonsillar growth.
  • Electroencephalogram [ Time Frame: every five weeks during each 20-week arm ] [ Designated as safety issue: No ]
    evaluates changes in epileptiform waves.
  • Scoliosis x-ray [ Time Frame: at the beginning and end of each 20-week arm ] [ Designated as safety issue: Yes ]
    determine if degree of scoliosis is affected by medication.
  • RNA profiling [ Time Frame: beginning and end of each 20-week arm ] [ Designated as safety issue: No ]
    The investigators will perform a genetic test to determine if the RNA profile of subjects is altered by the medication.
  • Mullen Scales of Early Learning [ Time Frame: beginning and end of each 20-week arm ] [ Designated as safety issue: No ]
    The investigators will administer this test to assess if the medication has an effect on cognition, motor function, and language skills.
  • Vineland Adaptive Behavior Scales [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: No ]
    This parental interview will be administered to determine if there is any change in subjects' adaptive behavior skills during the trial.
  • Clinical Global Impression Scales [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: No ]
  • Unified Parkinson Disease Rating Scale [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: No ]
  • Child Health Questionnaire [ Time Frame: beginning and end of each 20-week arm ] [ Designated as safety issue: No ]
    Child quality of life measure.
  • Your Health and Well-Being [ Time Frame: beginning and end of each 20-week arm ] [ Designated as safety issue: No ]
    Parental quality of life measure.
  • Stereotypy Linear Analog Scale [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: No ]
    Evaluates severity of stereotypical hand movements.
  • Rett Syndrome Behavior Questionnaire [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: No ]
  • Aberrant Behavior Checklist [ Time Frame: every five weeks during each 20 week arm ] [ Designated as safety issue: No ]
  • Parent Targeted Symptoms Visual Analog Scales [ Time Frame: Monthly ] [ Designated as safety issue: No ]
    Parent or caregiver selected target symptoms (3) measures on linear analog scale for duration of study

Estimated Enrollment:42
Study Start Date:December 2010
Estimated Study Completion Date:March 2014
Estimated Primary Completion Date:March 2013 (Final data collection date for primary outcome measure)
ArmsAssigned Interventions
Placebo Comparator: Saline placebo
Crossover study subjects will be randomized to receive twice daily subcutaneous injections (SC) of normal saline for a period of 20 weeks beginning with a sham dose escalation (40 µg/kg, 80 µg/kg, 120 µg/kg) over the first 3 weeks.
Drug: rhIGF-1
1) PHASE 1 (4 weeks): Subjects will receive escalating twice-daily doses of IGF-1 over 4 weeks (40 µg/kg, 80 µg/kg, 120 µg/kg) and then continue treatment at 120 µg/kg BID for 20 weeks should they choose to enroll in PHASE2.
Other Name: Mecasermin (brand name Increlex)
Active Comparator: rhIGF-1
PHASE 1: Subjects will receive escalating twice-daily doses of IGF-1 over 4 weeks (40 µg/kg, 80 µg/kg, 120 µg/kg) and then continue treatment at 120 µg/kg BID for 20 weeks should they choose to enroll in PHASE2.
  • ARM1: Crossover study subjects will be randomized to receive twice daily subcutaneous injections (SC) of IGF-1 or normal saline for a period of 20 weeks beginning with an initial or sham dose escalation (40 µg/kg, 80 µg/kg, 120 µg/kg) over the first 3 weeks. Subjects from PHASE1 will participate in every aspect of ARM1 of PHASE2; however, it will be open-label IGF-1 treatment and subjects will not participate in a placebo phase.
  • ARM2: After a 6 week wash-out period, the subjects will cross-over to the parallel arm and receive the alternate therapy (IGF-1 or normal saline) for an additional 20 week period, again beginning with an initial or sham dose escalation. Subjects enrolled in PHASE1 will not participate in ARM2.
Drug: rhIGF-1
1) PHASE 1 (4 weeks): Subjects will receive escalating twice-daily doses of IGF-1 over 4 weeks (40 µg/kg, 80 µg/kg, 120 µg/kg) and then continue treatment at 120 µg/kg BID for 20 weeks should they choose to enroll in PHASE2.
Other Name: Mecasermin (brand name Increlex)

Detailed Description:
There are two phases to the trial. Phase 1 is an intensive 6-week pharmacokinetic study which will require 3 inpatient stays and 4 half-day outpatient visits. During in-patient sessions, an IV line will be placed for frequent blood samples. A lumbar puncture will be performed by a physician at the beginning and again at the end of Phase 1. The primary goal of Phase 1 is to determine the safety of IGF-1 therapy for girls with RS. As such, the investigators will ask that you monitor your child's blood sugar levels using a glucometer. Your child's health is our utmost concern and she will be monitored continuously to ensure her safety. At the end of Phase 1, you will have the option of enrolling your daughter in an additional 20 weeks of treatment with IGF-1 during Phase 2 of the trial. The investigators must successfully complete Phase 1 before the investigators can move to the second phase of the trial with a larger number of patients.
The second phase will be double-blinded; meaning neither the families nor the researchers will know which participants are receiving IGF-1. The cross-over design of the trial means each subject will receive 20 weeks of either placebo or IGF-1 and then, after the 6-week washout period, participants will receive another 20 weeks of the alternate treatment. All girls enrolled in Phase 2 will receive 20 weeks of treatment with IGF-1.
Girls enrolled in Phase 2 will be seen monthly for safety monitoring, developmental evaluations and lab work. The investigators will ask caregivers to fill out a number of questionnaires and answer questions regarding their daughter's health, behavior and quality of life. The investigators will also monitor your daughter's heart function (ECG) and the electrical activity in her brain (EEG) four times throughout Phase 2. The BioRadio® is a child-friendly measurement device, capable of recording heart and breathing patterns. The investigators ask that your child wear the BioRadio® and Qsensor® for 2 hours of quiet activity during each study visit, every 5 weeks. Data from the BioRadio® will demonstrate if treatment with IGF-1 improves the heart rhythm and respiratory symptoms of girls with RS. Data from the Qsensor® may indicate if your child's perspiration level and body temperature show signs of normalizing.

Ages Eligible for Study:  2 Years to 12 Years
Genders Eligible for Study:  Female
Accepts Healthy Volunteers:  No
Inclusion Criteria:
  • female
  • with RTT (typical or variant) as defined using the internationally agreed 2010 RettSearch criteria.
  • genetically defined mutation or deletion of the MECP2 gene.
  • Girls will have the following prepubertal status: (1) Tanner stage 1 or 2 breast development; (2) Tanner stage 1 or 2 pubic hair development; (3) and younger than 12 years by bone age.
  • Chronological age must be 2 years or older
Exclusion Criteria:
  • prior therapeutic use of IGF-1, growth hormone, Lupron® or sex steroids
  • allergy to the trial product
  • co-morbid or chronic illness beyond that known to be associated with Rett Syndrome: diabetes mellitus, fatty acid oxidation disorder, chromosomal aneuploidy, syndromes associated with high risk of malignancy, current or previous exposure to spinal irradiation or history of malignancy.
  • severe scoliosis (defined as a spinal curve of 70 degrees or more as measured on clinical and radiological examination)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01253317

Contact: Kate V Barnes, BSc617-355-5230katherine.barnes@childrens.harvard.edu

United States, Massachusetts
Children's Hospital BostonRecruiting
Boston, Massachusetts, United States, 02115
Contact: Kate V Barnes, BSc     617-355-5230     katherine.barnes@childrens.harvard.edu    
Contact: Heather M O'Leary, BSc     617-355-2216     heather.oleary@childrens.harvard.edu    
Principal Investigator: Scott Pomeroy, MD, PhD            
Sponsors and Collaborators
Scott Pomeroy
International Rett Syndrome Foundation
Autism Speaks
Principal Investigator:Scott Pomeroy, MD, PhDChildren's Hospital Boston
Study Chair:Heather M O'Leary, BScChildren's Hospital Boston
  More Information

Additional Information:

No publications provided

Responsible Party:Scott Pomeroy, Neurologist-in-Chief, Children's Hospital, Boston
ClinicalTrials.gov Identifier:NCT01253317     History of Changes
Other Study ID Numbers:10-08-0403
Study First Received:December 2, 2010
Last Updated:March 19, 2012
Health Authority:United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:
Rett Syndrome

Additional relevant MeSH terms:
Rett Syndrome
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on May 24, 2012

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