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

Autism Clinical Trial

Official title:

Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01098383
• Other study ID #: SHEBA-09-7151-LG-CTIL
• Status: Recruiting
• Phase: Phase 4
• First received: March 11, 2010
• Last updated: October 13, 2016
• Start date: March 2010
• Est. completion date: December 2017

Study information

• Verified date: October 2016
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 18 Years

Eligibility

Inclusion criteria:

• 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.

Exclusion criteria:

• 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

• Epilepsy

• 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

Study Design

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

Related Conditions & MeSH terms

• Autism
• Autism Spectrum Disorder
• Autistic Disorder

Intervention

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.
• 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

Locations

Country	Name	City	State
Israel	Sheba Medical Center	Tel Hashomer	Ramat Gan

Sponsors (2)

Lead Sponsor	Collaborator
Sheba Medical Center	The Israeli Society of Clinical Pediatrics (HIPAK)

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Core autistic symptoms (ATEC)	The parents will fill out this questionnaire about their child once every 4 weeks during the first Phase (12 weeks)- the Treatment phase.	Once every 4 weeks during the first three mounth	No
Primary	Side effects and adverse events questionnaire	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.	Once every 4 weeks during the first phase(12 weeks)	Yes
Secondary	Linguistic performance (CELF-4)	The subject will be diagnosed on his Linguistic performance - using the CELF-4 diagnosis.	After 6 mounth of washout	No
Secondary	Adaptive functioning (Vineland-II)	The parents will be interviwed using the Adaptive functioning (Vineland-II)	After 6 mounth of washout	No
Secondary	Comorbid behaviors (CSI-4 questionnaire)	The parents will fill out the Comorbid behaviors (CSI-4) questionnaire	After 6 mouth of washout	No
Secondary	Executive functions (BRIEF questionnaire)	The parents will fill out the Executive functions (BRIEF) questionnaire.	After 6 mounth of washout	No