Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
Primary Purpose
Autism
Status
Unknown status
Phase
Phase 4
Locations
Israel
Study Type
Interventional
Intervention
Acetyl-Choline Esterase Inhibitors and Choline supplements
Indistinguishable placebo tablets, matching both donepezil and choline
Sponsored by
About this trial
This is an interventional treatment trial for Autism focused on measuring Autism
Eligibility Criteria
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
Sites / Locations
- Sheba Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo for AChEI and Choline
AChEI and Choline
Arm Description
Acetyl-choline Esterase Inhibitor and Choline supplements
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Linguistic performance (CELF-4)
The subject will be diagnosed on his Linguistic performance - using the CELF-4 diagnosis.
Adaptive functioning (Vineland-II)
The parents will be interviwed using the Adaptive functioning (Vineland-II)
Comorbid behaviors (CSI-4 questionnaire)
The parents will fill out the Comorbid behaviors (CSI-4) questionnaire
Executive functions (BRIEF questionnaire)
The parents will fill out the Executive functions (BRIEF) questionnaire.
Full Information
NCT ID
NCT01098383
First Posted
March 11, 2010
Last Updated
October 13, 2016
Sponsor
Sheba Medical Center
Collaborators
The Israeli Society of Clinical Pediatrics (HIPAK)
1. Study Identification
Unique Protocol Identification Number
NCT01098383
Brief Title
Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
Official Title
Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2010 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sheba Medical Center
Collaborators
The Israeli Society of Clinical Pediatrics (HIPAK)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism
Keywords
Autism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo for AChEI and Choline
Arm Type
Placebo Comparator
Arm Title
AChEI and Choline
Arm Type
Experimental
Arm Description
Acetyl-choline Esterase Inhibitor and Choline supplements
Intervention Type
Drug
Intervention Name(s)
Acetyl-Choline Esterase Inhibitors and Choline supplements
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Indistinguishable placebo tablets, matching both donepezil and choline
Intervention Description
Indistinguishable placebo tablets, matching both donepezil and choline, will be given in the same amounts and schedules
Primary Outcome Measure Information:
Title
Core autistic symptoms (ATEC)
Description
The parents will fill out this questionnaire about their child once every 4 weeks during the first Phase (12 weeks)- the Treatment phase.
Time Frame
Once every 4 weeks during the first three mounth
Title
Side effects and adverse events questionnaire
Description
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.
Time Frame
Once every 4 weeks during the first phase(12 weeks)
Secondary Outcome Measure Information:
Title
Linguistic performance (CELF-4)
Description
The subject will be diagnosed on his Linguistic performance - using the CELF-4 diagnosis.
Time Frame
After 6 mounth of washout
Title
Adaptive functioning (Vineland-II)
Description
The parents will be interviwed using the Adaptive functioning (Vineland-II)
Time Frame
After 6 mounth of washout
Title
Comorbid behaviors (CSI-4 questionnaire)
Description
The parents will fill out the Comorbid behaviors (CSI-4) questionnaire
Time Frame
After 6 mouth of washout
Title
Executive functions (BRIEF questionnaire)
Description
The parents will fill out the Executive functions (BRIEF) questionnaire.
Time Frame
After 6 mounth of washout
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lidia Gabis, MD
Organizational Affiliation
Sheba Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dorit Ben-Shalom, Ph.D
Organizational Affiliation
Ben-Gurion University of the Negev
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Shefer Shahar, Dr.
Organizational Affiliation
Sheba Medical Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Rotem Chayu Ben-Hur, MA
Organizational Affiliation
Sheba Medical Center
Official's Role
Study Director
Facility Information:
Facility Name
Sheba Medical Center
City
Tel Hashomer
State/Province
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shahar Shefer, Dr
Phone
+972-(0)54-4381594
Email
DRShahar.Shefer@sheba.health.gov.il
First Name & Middle Initial & Last Name & Degree
Maaian Millikovsky, BA
12. IPD Sharing Statement
Learn more about this trial
Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
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