Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
Information source: Sheba Medical Center
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Autism
Intervention: Acetyl-Choline Esterase Inhibitors and Choline supplements (Drug); Indistinguishable placebo tablets, matching both donepezil and choline (Drug)
Phase: Phase 4
Sponsored by: Sheba Medical Center
Official(s) and/or principal investigator(s):
Lidia Gabis, MD, Principal Investigator, Affiliation: Sheba Medical Center
Dorit Ben-Shalom, Ph.D, Study Director, Affiliation: Ben-Gurion University of the Negev
Shefer Shahar, Ph.D, Study Director, Affiliation: Sheba Medical Center
Rotem Chayu Ben-Hur, MA, Study Director, Affiliation: Sheba Medical Center
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.
Official title: Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Core autistic symptoms (ATEC)
Side effects and adverse events questionnaire
Linguistic performance (CELF-4)
Adaptive functioning (Vineland-II)
Comorbid behaviors (CSI-4 questionnaire)
Executive functions (BRIEF questionnaire)
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.
Minimum age: 10 Years.
Maximum age: 18 Years.
- A formal diagnosis of Autism or Pervasive Developmental Disorder not otherwise
specified (PDD-NOS), given by a child neurologist.
- Age: 10-18 years.
- A signed parental consent form.
- Evidence for one of the following conditions:
- an underlying infectious disease
- chromosomal abnormality
- metabolic disorder
- specific brain related disorder (such as tuberous sclerosis)
- history of fetal cytomegalovirus infection
- birth asphyxia
- a history of major head injury
- a chronic use of non-steroidal anti-inflammatory drugs, (NSAID)
- known brain damage
- Abnormal Electro-cardiogram (ECG)
- Epileptiform EEG
- Use of psychostimulants, anti-depressants, neuroleptics or anti-convulsive agents
within the past month.
- Lack of cooperation in the screening phase
Locations and Contacts
Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel; Recruiting
Shahar Shefer, Dr, Phone: +972-(0)54-4381594, Email: DRShahar.Shefer@sheba.health.gov.il
Maaian Millikovsky, BA, Sub-Investigator
Starting date: March 2010
Last updated: July 19, 2012