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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01098383
Recruitment Status : Unknown
Verified October 2016 by Dr. Lidia Gabis MD, Sheba Medical Center.
Recruitment status was:  Recruiting
First Posted : April 2, 2010
Last Update Posted : October 14, 2016
Sponsor:
Collaborator:
The Israeli Society of Clinical Pediatrics (HIPAK)
Information provided by (Responsible Party):
Dr. Lidia Gabis MD, Sheba Medical Center

Tracking Information
First Submitted Date  ICMJE March 11, 2010
First Posted Date  ICMJE April 2, 2010
Last Update Posted Date October 14, 2016
Study Start Date  ICMJE March 2010
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2010)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01098383 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2010)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
Official Title  ICMJE Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Autism
Intervention  ICMJE
  • 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.

  • 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
Study Arms  ICMJE
  • Placebo Comparator: Placebo for AChEI and Choline
    Intervention: Drug: Indistinguishable placebo tablets, matching both donepezil and choline
  • Experimental: AChEI and Choline
    Acetyl-choline Esterase Inhibitor and Choline supplements
    Intervention: Drug: Acetyl-Choline Esterase Inhibitors and Choline supplements
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 1, 2010)
84
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01098383
Other Study ID Numbers  ICMJE SHEBA-09-7151-LG-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Lidia Gabis MD, Sheba Medical Center
Study Sponsor  ICMJE Sheba Medical Center
Collaborators  ICMJE The Israeli Society of Clinical Pediatrics (HIPAK)
Investigators  ICMJE
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
PRS Account Sheba Medical Center
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP