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

NCT01098383 | Unknown Phase 4

• 1 other identifier: SHEBA-09-7151-LG-CTIL
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism

Keywords

Autism

Outcome Measures

Primary Outcomes (2)

• 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

• 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)

Secondary Outcomes (4)

• Linguistic performance (CELF-4)

  After 6 mounth of washout

• Adaptive functioning (Vineland-II)

  After 6 mounth of washout

• Comorbid behaviors (CSI-4 questionnaire)

  After 6 mouth of washout

• Executive functions (BRIEF questionnaire)

  After 6 mounth of washout

Study Arms (2)

Placebo for AChEI and Choline

PLACEBO COMPARATOR

Drug: Indistinguishable placebo tablets, matching both donepezil and choline

AChEI and Choline

EXPERIMENTAL

Acetyl-choline Esterase Inhibitor and Choline supplements

Drug: Acetyl-Choline Esterase Inhibitors and Choline supplements

Interventions

Acetyl-Choline Esterase Inhibitors and Choline supplements DRUG

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.

AChEI and Choline

Indistinguishable placebo tablets, matching both donepezil and choline DRUG

Indistinguishable placebo tablets, matching both donepezil and choline, will be given in the same amounts and schedules

Placebo for AChEI and Choline

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sheba Medical Center: lead
• The Israeli Society of Clinical Pediatrics (HIPAK): collaborator

Study Sites (1)

Sheba Medical Center

Tel Litwinsky, Ramat Gan, 52621, Israel

RECRUITING

Related Publications (2)

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

• Ure A, Cox GR, Haslam R, Williams K. Acetylcholinesterase inhibitors for autistic spectrum disorders. Cochrane Database Syst Rev. 2023 Jun 1;6(6):CD013851. doi: 10.1002/14651858.CD013851.pub2.

  PMID: 37267443 DERIVED

MeSH Terms

Conditions

Autistic Disorder

Interventions

Choline

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds

Study Officials

• Lidia Gabis, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Lidia Gabis

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: April 2, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: October 14, 2016

Record last verified: 2016-10

Locations

IL (1)