Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders

Phase 4

• Conditions: Autism
• Interventions: Drug: Indistinguishable placebo tablets, matching both donepezil and choline; Drug: Acetyl-Choline Esterase Inhibitors and Choline supplements

• Registration Number: NCT01098383
• Lead Sponsor: Sheba Medical Center

Brief Summary

We propose a study which will combine multiple modalities in evaluating the treatment response of children with autism spectrum disorders (ASD) to acetyl-choline esterase (AChE) inhibitors and choline supplements. The primary objective of the study is to examine the efficacy of this treatment in improving core autistic symptoms. The Secondary objective of the study is to evaluate the safety and tolerability of the treatment protocol in ASD children. Exploratory objectives include evaluation of the influence of the treatment on linguistic performance, comorbid behaviors, adaptive functioning and executive functions.

Detailed Description

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.

Study Timeline

• Study Start: 2010-03
• Study First Submitted: 2010-03-11
• Study First Submitted QC: 2010-04-01
• Study First Posted: 2010-04-02
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-13
• Last Update Posted: 2016-10-14
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo for AChEI and Choline	Indistinguishable placebo tablets, matching both donepezil and choline	-
AChEI and Choline	Acetyl-Choline Esterase Inhibitors and Choline supplements	Acetyl-choline Esterase Inhibitor and Choline supplements

Primary Outcome Measures

Name	Time	Method
Side effects and adverse events questionnaire	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.
Core autistic symptoms (ATEC)	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.

Secondary Outcome Measures

Name	Time	Method
Linguistic performance (CELF-4)	After 6 mounth of washout	The subject will be diagnosed on his Linguistic performance - using the CELF-4 diagnosis.
Comorbid behaviors (CSI-4 questionnaire)	After 6 mouth of washout	The parents will fill out the Comorbid behaviors (CSI-4) questionnaire
Executive functions (BRIEF questionnaire)	After 6 mounth of washout	The parents will fill out the Executive functions (BRIEF) questionnaire.
Adaptive functioning (Vineland-II)	After 6 mounth of washout	The parents will be interviwed using the Adaptive functioning (Vineland-II)

Trial Locations

Locations (1)

Sheba Medical Center; 🇮🇱 Tel Hashomer, Ramat Gan, Israel