Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
|Autism||Drug: Acetyl-Choline Esterase Inhibitors and Choline supplements Drug: Indistinguishable placebo tablets, matching both donepezil and choline||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism|
- Core autistic symptoms (ATEC) [ Time Frame: Once every 4 weeks during the first three mounth ]The parents will fill out this questionnaire about their child once every 4 weeks during the first Phase (12 weeks)- the Treatment phase.
- Side effects and adverse events questionnaire [ Time Frame: Once every 4 weeks during the first phase(12 weeks) ]A detailed parent questionnaire to assess side effects and adverse events. The parents will fill out these questionnaires about their child once every 4 weeks during the first phase(12 weeks)- which is the treatment phase.
- Linguistic performance (CELF-4) [ Time Frame: After 6 mounth of washout ]The subject will be diagnosed on his Linguistic performance - using the CELF-4 diagnosis.
- Adaptive functioning (Vineland-II) [ Time Frame: After 6 mounth of washout ]The parents will be interviwed using the Adaptive functioning (Vineland-II)
- Comorbid behaviors (CSI-4 questionnaire) [ Time Frame: After 6 mouth of washout ]The parents will fill out the Comorbid behaviors (CSI-4) questionnaire
- Executive functions (BRIEF questionnaire) [ Time Frame: After 6 mounth of washout ]The parents will fill out the Executive functions (BRIEF) questionnaire.
|Study Start Date:||March 2010|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo for AChEI and Choline||
Drug: Indistinguishable placebo tablets, matching both donepezil and choline
Indistinguishable placebo tablets, matching both donepezil and choline, will be given in the same amounts and schedules
Experimental: AChEI and Choline
Acetyl-choline Esterase Inhibitor and Choline supplements
Drug: Acetyl-Choline Esterase Inhibitors and Choline supplements
Donepezil will be used at initial dose of 2.5 mg/day (during the first two weeks), and an increased dose of 5 mg/day (from the 3rd week and on), according to the treatment protocol listed below. The tablets will be taken during breakfast.
AChE inhibitors are considered as potent agents for clinical use in Alzheimer's and Parkinson's dementias (Wevers & Schroder, 1999) and treatment with these agents was proven to be well-tolerated, safe and effective in these populations. Cholinergic side effects are generally transient, mild and dose-related, and primarily include diarrhea, nausea, and vomiting.
Choline tablets will be taken at daily doses of 250 mg (in children with up to 40 kg body weight) and 500 mg (in children with more than 40 kg body weight), based on half of the adult daily dose.
Autism Spectrum Disorders (ASD) are a group of developmental disorders of brain function resulting in a distinct phenotype, most probably related to many specific causes. Individuals with a disorder in the autism spectrum are a heterogeneous group of patients with early childhood onset of deficits in social interaction, communication and language, and repetitive and stereotypic behaviors. ASD has become increasingly prevalent during the last few decades (Wiznitzer, 2005).
The neuro-anatomical substrate of ASD has been the subject of intense investigation, but current findings are inconclusive, limited and sometimes even contradictory.
Medical treatment of autism is still a matter of dispute. Medications used are mainly aimed to treat the comorbid symptoms, such as epilepsy, tics, obsessive-compulsive or hyperactive behaviors (Wiznitzer, 2005). Although many efforts were invested in establishing a model of autistic pathophysiology, no such model is currently accepted, and there is no evidence for an efficient treatment of the core autistic symptoms (Wiznitzer, 2005).
Previous studies indicate that many brain systems are involved in the expression of autism. Specifically, it has been suggested that autism involves neurotransmitter dysregulations (Lam et al, 2006). A recent investigation of the cholinergic system in autism, detailed below, has provided promising findings. Our study aims to assess the clinical outcomes associated with cholinergic manipulations using pharmacological agents and nutritional supplements. The study approved by the Helsinki committee for clinical research.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01098383
|Sheba Medical Center||Recruiting|
|Tel Hashomer, Ramat Gan, Israel, 52621|
|Contact: Shahar Shefer, Dr +972-(0)54-4381594 DRShahar.Shefer@sheba.health.gov.il|
|Sub-Investigator: Maaian Millikovsky, BA|
|Principal Investigator:||Lidia Gabis, MD||Sheba Medical Center|
|Study Director:||Dorit Ben-Shalom, Ph.D||Ben-Gurion University of the Negev|
|Study Director:||Shefer Shahar, Dr.||Sheba Medical Center|
|Study Director:||Rotem Chayu Ben-Hur, MA||Sheba Medical Center|