Some children with autism show symptom improvement by 6 years old - Early diagnosis associated with likelihood of improvement

A study shows that over 10% of children with autism show improvement with their symptoms by age 6.  20% improve in adaptive functioning. 

Here is the most interesting finding " The earlier the children were diagnosed, the more likely they were to show improvement in functioning, the study found."

Please ask friends, family and physicians to encourage the earliest possible diagnosis.

JR

More than 10 percent of preschool-age children diagnosed with autism saw some improvement in their symptoms by age 6. And 20 percent of the children made some gains in everyday functioning, a new study found.

Canadian researchers followed 421 children from diagnosis (between ages 2 and 4) until age 6, collecting information at four points in time to see how their symptoms and their ability to adapt to daily life fared.

"Between 11 and 20 percent did remarkably well," said study leader Dr. Peter Szatmari, chief of the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health in Toronto.

However, improvement in symptom severity wasn't necessarily tied to gains in everyday functioning, Szatmari said. Eleven percent of the children experienced some improvement in symptoms. About 20 percent improved in what experts call "adaptive functioning" -- meaning how they function in daily life. These weren't necessarily the same children, he said.

"You can have a child over time who learns to talk, socialize and interact, but still has symptoms like flapping, rocking and repetitive speech," Szatmari said. "Or you can have kids who aren't able to talk and interact, but their symptoms like flapping reduce remarkably over time."

The interplay between these two areas -- symptom severity and ability to function -- is a mystery, and should be the topic of more research, Szatmari said.

One take-home point of the research, Szatmari said, is that there's a need to address both symptoms and everyday functioning in children with autism spectrum disorder.

"If it were my kid, I would want adaptive functioning to improve and [feel] symptoms are less important," he said. "Adaptive functioning determines your place in the world."

Only 66 of the study participants were girls, and Szatmari found they had less severe symptoms and more improvement in symptoms than boys. The earlier the children were diagnosed, the more likely they were to show improvement in functioning, the study found.

The findings were published online Jan. 28 in the journal JAMA Psychiatry.

About 1 in 68 children in the United States is affected by autism spectrum disorder (ASD), and boys more so than girls, according to the U.S. Centers for Disease Control and Prevention. ASD is a group of developmental disabilities marked by social, communication and behavioral difficulties. Symptoms can range from mild to severe, and the condition is thought to be lifelong.

Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Cohen Children's Medical Center of New York in New Hyde Park, N.Y., called the new research well done and said it yielded some important points for parents and doctors.

"This study highlights not only the variability of autism symptom severity among young children with ASD, but also the variability in adaptive functioning such as self-care skills," said Adesman, who wasn't involved in the study.

For parents discouraged by the relatively small percentage of children in the study who showed improvement in either area, Adesman noted that kids diagnosed earlier with autism may be more severely affected. Also, parents shouldn't generalize the study findings to children who are older when diagnosed, as they may be less severely affected, he said.

Szatmari added that parents who suspect their child shows symptoms of autism, such as an inability to interact or speak properly, should seek an evaluation.

Read more here

Is their a link between autism and lyme disease? No.

Some patients have asked about a link between autism and lyme disease. There does not appear to be a significant link. - JR

Autism-Lyme 

Correlation Debunked

Researchers find zero evidence for Lyme-induced autism.

WIKIMEDIA, SCOTT BAUER, USDA

The hypothesized link between autism and Lyme disease loses ground with a new study that found no evidence of an infection in patients with the social development disorder. The results, published today (April 30) in the Journal of the American Medical Association, imply that antibiotics against the Lyme disease pathogen—a popular new strategy for autism—will not ameliorate most patients’ symptoms.

“The data don’t address whether a single case of autism was ever caused by Lyme disease, but it rules out the suggestion that it does so with any frequency,” said Armin Alaedini, an immunologist at Columbia University Medical Center in New York and an author on the study. “I think that for me, this is the end of looking into the link between autism and Lyme.”  

In recent years, some doctors have anecdotally noted that many of their autism patients have Lyme disease. Two small studies listed in a booklet from a 2007 meeting of the Lyme-Induced Autism Foundation, a Corona, California-based organization that advocates an “eclectic healing approach,” reported that 1 in 5 autistic patients had the tick-borne disease. Websites on the topic now put that number closer to 9 out of 10. These statistics, however, have not been peer-reviewed. Nonetheless, some doctors prescribe antibiotics to autistic children and say the therapy quells their symptoms.

To systematically assess the prevalence of Lyme disease among people with autism, Armin Alaedini, an immunologist at Columbia University Medical Center in New York, and his colleagues analyzed blood samples from 120 children and teens: 70 participants had autism, and 50 served as healthy controls. Alaedini looked for antibodies against the bacterium underlying Lyme, Borrelia burgdorferi, and found that not a single participant tested positive for the infection.

“This means that you wouldn’t see 20 percent of children with autism getting their disease from Lyme,” Alaedini said. He entered into the study objectively, he said, wanting to explore a correlation that had gained traction among doctors and the public. “Autism has become a hot topic, and a lot of people are publishing findings that are bogus but still alarm parents.”

M. Ajamian et al., “Serologic markers of Lyme disease in children with autism,” Journal of the American Medical Association, 309: 1771-72, 2013.

Link to article here

Reaching My Autistic Son Through Disney

What an amazing story about meeting a child where he is. JR

In our first year in Washington, our son disappeared.

Just shy of his 3rd birthday, an engaged, chatty child, full of typical speech — “I love you,” “Where are my Ninja Turtles?” “Let’s get ice cream!” — fell silent. He cried, inconsolably. Didn’t sleep. Wouldn’t make eye contact. His only word was “juice.”

I had just started a job as The Wall Street Journal’s national affairs reporter. My wife, Cornelia, a former journalist, was home with him — a new story every day, a new horror. He could barely use a sippy cup, though he’d long ago graduated to a big-boy cup. He wove about like someone walking with his eyes shut. “It doesn’t make sense,” I’d say at night. “You don’t grow backward.” Had he been injured somehow when he was out of our sight, banged his head, swallowed something poisonous? It was like searching for clues to a kidnapping.

After visits to several doctors, we first heard the word “autism.” Later, it would be fine-tuned to “regressive autism,” now affecting roughly a third of children with the disorder. Unlike the kids born with it, this group seems typical until somewhere between 18 and 36 months — then they vanish. Some never get their speech back. Families stop watching those early videos, their child waving to the camera. Too painful. That child’s gone.

In the year since his diagnosis, Owen’s only activity with his brother, Walt, is something they did before the autism struck: watching Disney movies. “The Little Mermaid,” “Beauty and the Beast,” “Aladdin” — it was a boom time for Disney — and also the old classics: “Dumbo,” “Fantasia,” “Pinocchio,” “Bambi.” They watch on a television bracketed to the wall in a high corner of our smallish bedroom in Georgetown. It is hard to know all the things going through the mind of our 6-year-old, Walt, about how his little brother, now nearly 4, is changing. They pile up pillows on our bed and sit close, Walt often with his arm around Owen’s shoulders, trying to hold him — and the shifting world — in place.

Photo

Owen at 18 months, before signs of autism.CreditFrom the Suskind family

Then Walt slips out to play with friends, and Owen keeps watching. Movie after movie. Certain parts he rewinds and re-watches. Lots of rewinding. But he seems content, focused.

We ask our growing team of developmental specialists, doctors and therapists about it. We were never big fans of plopping our kids in front of Disney videos, but now the question seemed more urgent: Is this good for him? They shrug. Is he relaxed? Yes. Does it seem joyful? Definitely. Keep it limited, they say. But if it does all that for him, there’s no reason to stop it.

So we join him upstairs, all of us, on a cold and rainy Saturday afternoon in November 1994. Owen is already on the bed, oblivious to our arrival, murmuring gibberish. . . . “Juicervose, juicervose.” It is something we’ve been hearing for the past few weeks. Cornelia thinks maybe he wants more juice; but no, he refuses the sippy cup. “The Little Mermaid” is playing as we settle in, propping up pillows. We’ve all seen it at least a dozen times, but it’s at one of the best parts: where Ursula the sea witch, an acerbic diva, sings her song of villainy, “Poor Unfortunate Souls,” to the selfish mermaid, Ariel, setting up the part in which Ursula will turn Ariel into a human, allowing her to seek out the handsome prince, in exchange for her voice.

Full article here

Brain differences in those with Autism: Think Local Not Global

A new study shows that a person with autism's brain is wired differently than those without autism, and this finding may help explain some of the typical symptoms of autism. 

Increased connectivity may favor local connections over global. - JR

The way the gray matter in the brain is wired appears to be different in people with autism, new research shows.

Specifically, those with the disorder are more likely to have enhanced connections in the brain that are associated with common autism symptoms, such as narrow interests and repetitive behaviors, the scientists reported.

"Our study [and others] reliably and repeatedly demonstrate that the brain in autism is built and functions differently, which explains a variety of autistic symptoms," said study author Christine Ecker, a lecturer in neuroimaging at King's College London.

"From neuropsychology, we also know that people with autism often have a preference for processing [fine details] over global features (the ability to integrate piecemeal information into a coherent whole)," she said. "Our findings may therefore represent a neuroanatomical correlate of these behaviors, although a direct causal link remains to be established."

Results of the study were published online July 22 in the Proceedings of the National Academy of Sciences.

Autism spectrum disorders are a group of neurodevelopmental disorders, common symptoms of which include impaired social communication, social reciprocity and repetitive behaviors, according to background information included in the study. Experts believe that differences in the brain account for these behaviors, but the exact changes that might occur in someone with autism aren't yet clear, according to the study.

The current study looked at 34 adult males with autism and 34 males without autism to serve as the control group. All of the study volunteers underwent MRI.

The researchers found that there were significant differences in the length of the connections between regions of the brain when they compared people with autism to those without. The minimum length of these connections in the cortical gray matter was dubbed "wiring costs" by the researchers. These wiring costs were significantly reduced in people with autism, meaning the lengths of their connections were shorter.

"These differences are predominantly observed in brain regions that we know are anatomically different in autism, and that are underlying autistic symptoms and traits," Ecker said. "We think that such differences in neuronal wiring may lead to locally over-connected networks in the brains of [patients with autism spectrum disorders] that could explain some autistic symptoms, such as repetitive behaviors."

One expert said the findings help define the biological basis of autism more clearly.

"We've known that there is a history of wiring differences that appear in individuals with autism. What's novel is that they used structural imaging to assess whether neurons are connected in the same way structurally," said Daniel Smith, senior director of discovery neuroscience at Autism Speaks.

"Gray matter connections are referred to as microcircuits, and they're everywhere," Smith said. "They're very important in the cerebral cortex, and the highest levels of thinking occur in the cerebral cortical regions of the brain."

"This study is another component in building our knowledge base," he added. "It's a step toward better understanding of what's happening in the brain and, ultimately, that will help lead to new treatments. But this study won't lead to an immediate impact on treatment."

Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at the Steven and Alexandra Cohen Children's Medical Center in New Hyde Park, N.Y., agreed that this study won't lead to any immediate changes in the field.

"Unfortunately, despite the many advances in our ability to study the brain and identify a range of structural and functional differences associated with autism, we are still left with more questions than answers," Adesman said.

"[But] studies such as this bring us one step closer to understanding the neurobiological underpinnings of the mysterious and enigmatic condition known as autism spectrum disorder," he said.

Ecker said she hopes to conduct a study that follows young people as their brains are developing to see how the connections in the brain behave over time in people with autism.

Read more here

Full article

This is an evidence-based article on autism treatment. JR

New Hope for Autistic Children Who Never Learn to Speak

Apr. 24, 2013 — An Autistica consultation published this month found that 24% of children with autism were non-verbal or minimally verbal, and it is known that these problems can persist into adulthood.

Professionals have long attempted to support the development of language in these children but with mixed outcomes. An estimated 600,000 people in the UK and 70 million worldwide have autism, a neuro-developmental condition which is life-long.

Today, scientists at the University of Birmingham publish a paper in Frontiers in Neuroscience showing that while not all of the current interventions used are effective, there is real hope for progress by using interventions based on understanding natural language development and the role of motor and "motor mirroring" behaviour in toddlers.

The researchers, led by Dr Joe McCleery, who is supported by autism research charity Autistica, examined over 200 published papers and more than 60 different intervention studies, and found that:

• Motor behaviours, such as banging toys and copying gestures or facial expressions ("mirroring"), play a key role in the learning of language.
• Children with autism show specific motor impairments, and less "mirroring" brain activity, particularly in relation to strangers in whom they show very little interest. This finding may hold the key to language problems overall.
• Despite extensive use of sign language training to improve speech and communication skills in non-verbal children with autism, there is very little evidence that it makes a positive impact, potentially due to the impairments in motor behaviours and mirroring.
• Picture exchange training can lead to improvements in speech. Here, children gradually learn to "ask" for things by exchanging pictures. This may work well because it does not depend on complex motor skills or mirroring.
• Play-based approaches which employ explicit teaching strategies and are developmentally based are particularly successful.
• New studies involving a focus on motor skills alongside speech and language intervention are showing promising preliminary results. This is exciting because these interventions utilise our new understanding of the role of motor behaviours in the development of speech and social interaction.

...

Christine Swabey, CEO of Autistica, says: "80% of the parents in our recent consultation wanted interventions straight after diagnosis. Dr McCleery's work shows how critical it is for all intervention to be evidence-based, and that the best approaches are based on a real understanding of the development of difficulties in autism. We are proud to be supporting the next steps in this vital research which will improve the quality of life for people with autism."

Alison Hardy, whose son Alfie is six, says: "As a parent of an autistic child, who is non-verbal, I feel quite vulnerable. People are always saying "try this, it worked wonders for us." But you can't try everything. We need a proper, scientific evidence base for what works and what does not. Then we can focus our time and our effort, with some confidence that we have a chance of helping our children."

link here

Thinking the Unthinkable - I am Adam Lanza's Mother

Families are in this situation all the time. - JR

I am Adam Lanza’s Mother

It's time to talk about mental illness

Thinking the Unthinkable

Michael holding a butterfly

In the wake of another horrific national tragedy, it’s easy to talk about guns. But it’s time to talk about mental illness.

Three days before 20 year-old Adam Lanza killed his mother, then opened fire on a classroom full of Connecticut kindergartners, my 13-year old son Michael (name changed) missed his bus because he was wearing the wrong color pants.

“I can wear these pants,” he said, his tone increasingly belligerent, the black-hole pupils of his eyes swallowing the blue irises.

“They are navy blue,” I told him. “Your school’s dress code says black or khaki pants only.”

“They told me I could wear these,” he insisted. “You’re a stupid bitch. I can wear whatever pants I want to. This is America. I have rights!”

“You can’t wear whatever pants you want to,” I said, my tone affable, reasonable. “And you definitely cannot call me a stupid bitch. You’re grounded from electronics for the rest of the day. Now get in the car, and I will take you to school.”

I live with a son who is mentally ill. I love my son. But he terrifies me.

A few weeks ago, Michael pulled a knife and threatened to kill me and then himself after I asked him to return his overdue library books. His 7 and 9 year old siblings knew the safety plan—they ran to the car and locked the doors before I even asked them to. I managed to get the knife from Michael, then methodically collected all the sharp objects in the house into a single Tupperware container that now travels with me. Through it all, he continued to scream insults at me and threaten to kill or hurt me.

That conflict ended with three burly police officers and a paramedic wrestling my son onto a gurney for an expensive ambulance ride to the local emergency room. The mental hospital didn’t have any beds that day, and Michael calmed down nicely in the ER, so they sent us home with a prescription for Zyprexa and a follow-up visit with a local pediatric psychiatrist.

We still don’t know what’s wrong with Michael. Autism spectrum, ADHD, Oppositional Defiant or Intermittent Explosive Disorder have all been tossed around at various meetings with probation officers and social workers and counselors and teachers and school administrators. He’s been on a slew of antipsychotic and mood altering pharmaceuticals, a Russian novel of behavioral plans. Nothing seems to work.

At the start of seventh grade, Michael was accepted to an accelerated program for highly gifted math and science students. His IQ is off the charts. When he’s in a good mood, he will gladly bend your ear on subjects ranging from Greek mythology to the differences between Einsteinian and Newtonian physics to Doctor Who. He’s in a good mood most of the time. But when he’s not, watch out. And it’s impossible to predict what will set him off.  

Several weeks into his new junior high school, Michael began exhibiting increasingly odd and threatening behaviors at school. We decided to transfer him to the district’s most restrictive behavioral program, a contained school environment where children who can’t function in normal classrooms can access their right to free public babysitting from 7:30-1:50 Monday through Friday until they turn 18.

More here 

Children With Autism go to Emergency Room Nine Times More Than Peers

We work very hard to keep children with autism and neuropsychiatric / neurobehavioral problems out of emergency rooms.  Early recognition and treatment often avoids emergencies. JR


A study showed that children with autism are nine times more likely to show up at the emergency room with a psychiatric condition than other children.

In the first study to compare mental health-related emergency department (ED) visits between children with and without autism spectrum disorders (ASD), researchers found that ED visits are nine times more likely to be for psychiatric reasons if a child has an ASD diagnosis. Published in the journalPediatric Emergency Care (Epub ahead of print), the study found externalizing symptoms, such as severe behaviors tied to aggression, were the leading cause of ED visits among children with ASD. Importantly, the likelihood of a psychiatric ED visit was higher if a child carried private health insurance rather than medical assistance.

"This finding of higher rates of emergency room visits among children with autism demonstrates that many children with autism aren't receiving sufficient outpatient mental health care to prevent and manage the type of crises that are driving these families to seek urgent help," said Dr. Roma Vasa, senior study author and a child psychiatrist in Kennedy Krieger Institute's Center for Autism & Related Disorders. "These findings should highlight the urgent need for better comprehensive outpatient mental health care and insurance coverage for children with autism, along with greater education and training for emergency medical staff."

Using the 2008 National Emergency Department Sample, the largest all-payer ED database in the US, researchers examined data from a total of 3,974,332 ED visits for patients ages 3 to 17, of which 13,191 visits were from children with ASD. Mental health-related ED visits were based on International Classification of Disease (ICD) billing diagnoses that included mood, anxiety and psychotic disorders, suicide and self-injury, and externalizing behaviors such as aggression.

Researchers also studied the influence of different types of insurance coverage on the likelihood of an ED visit for psychiatric reasons. They found that children with ASD whose families had private medical insurance were 58 percent more likely to visit the ED for mental health-related reasons than those whose health insurance was provided through state medical assistance programs.

"We think this is because private insurance plans often exclude autism from behavioral health coverage, have few in-network providers or place restrictive limits on the amount of mental health expenses that they will reimburse," said Luther Kalb, MHS, first study author and a research scientist in Kennedy Krieger Institute's Center for Autism & Related Disorders.

With 1 in 88 children in the U.S. diagnosed with ASD, the use of the ED to treat psychiatric behaviors is likely to increase unless changes occur. Dr. Vasa suggests that this trend is especially troublesome because the ED is not an optimal setting for children with ASD since chaotic environments can exacerbate autism-related or comorbid psychiatric symptoms.

"Children with autism, especially those with co-occurring psychotic disorders or severe behaviors, need to have an emergency crisis plan in place," said Kalb. "Everyone involved in the life of a child with autism, from parents to medical professionals to school educators, needs to have routine discussions about what to do in the case of an escalating situation."

This study also suggests that emergency departments should consider adopting new measures to accommodate children with ASD. This includes greater education and training for ED professionals about how to properly assess and interact with children on the autism spectrum. Additionally, researchers suggest that the large numbers of children with autism accessing the ED may necessitate a separate area for children with ASD that is less chaotic and contains less stimulation than found in the otherwise busiest part of any hospital.

Further research on adults with ASD using the ED for psychiatric reasons and general trends associated with mental health care is needed. With more information, medical professionals and insurance providers can have a greater understanding of the gaps in care and work to improve services.

Read more here

SENSORY FRIENDLY ACCESS EVENTS at CHILDRENS MUSEUM

SENSORY FRIENDLY ACCESS

JOIN US FOR OUR NEXT SENSORY FRIENDLY EVENTS!

MONDAY, NOVEMBER 5, 2012
4-8 PM
 
MONDAY, FEBRUARY 18, 2013
10AM-2PM
 
MONDAY, APRIL 22, 2013
4-8 PM

ONLY $5!

Sensory Friendly Day is an opportunity for kids with Autism Spectrum Disorders (ASD) to explore the Children’s Museum of Houston in their own way and in their own time!

These exclusive events will:

•Provide a comfortable, protected and accepting environment.
•Allow parents to make connections with other families.
•Offer new tools and resources.

Doors will be closed to the general public.
There will be no music.
Sound reducing headphones will be available.
Fresh Café will be closed, so feel free to bring your own food if needed.

To register, please contact Lydia Dungus at (713) 535-7238.
For more information, please contact Will Rice at (713-)535-7286.

The Children’s Museum of Houston is committed to making our Museum accessible and interactive for all. Below you will find useful information for planning a more comfortable and enjoyable visit with your family.

Click Here for More

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

  Purpose

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.

Condition	Intervention	Phase
Rett Syndrome	Drug: rhIGF-1	Phase 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
Official Title:	PHARMACOLOGICAL TREATMENT OF RETT SYNDROME BY STIMULATION OF SYNAPTIC MATURATION WITH IGF-1

Resource links provided by NLM:

Genetics Home Reference related topics: MECP2 duplication syndrome PPM-X syndrome

MedlinePlus related topics: Rett Syndrome

Drug Information available for: Insulin-like growth factor I Mecasermin

U.S. FDA Resources 

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)

Arms	Assigned 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. PHASE 2: 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.

  Eligibility

Ages Eligible for Study:	2 Years to 12 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts

Contact: Kate V Barnes, BSc

617-355-5230

katherine.barnes@childrens.harvard.edu

Locations

United States, Massachusetts
Children's Hospital Boston	Recruiting
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

Investigators

Principal Investigator:	Scott Pomeroy, MD, PhD	Children's Hospital Boston
Study Chair:	Heather M O'Leary, BSc	Children's Hospital Boston

  More Information

Additional Information:

Related Info  

Related Info  

Related Info  

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 IGF-1 Increlex Mecasermin

IGF1 MECP2 RTT

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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