Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety and efficacy of mecamylamine for the core symptoms of autism.

Detailed Description
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This is a placebo-controlled pilot clinical trial of a nicotinic agent based on evidence that a disturbance occurs in nicotinic cholinergic transmission in the brain of autistic children. This pharmacotherapeutic trial will be conducted as a direct result of findings of a nicotinic receptor abnormality in autopsied brain tissue from individuals who suffered from autism. A pharmacological agent, mecamylamine, with specificity for the nicotinic receptors implicated in autism, will be tested in children with autism spectrum disorder. Twenty children who meet inclusion/exclusion criteria will be randomized in a 2:3 ratio to 14 weeks of either matched placebo (n=8) or mecamylamine (n=12). Children randomized to placebo who do not respond will be given the opportunity to enroll in a ten week open label extension. The trial has been completed and published in J. of Child & Adolescent Psychopharmacology.

Official Title
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Neuronal Nicotinic Receptor Modulation in the Treatment of Autism: A Pilot Trial of Mecamylamine

Conditions
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Autistic Disorder, Pervasive Developmental Disorder

Intervention / Treatment
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* Drug: mecamylamine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified Age 4-12 General good health IQ of >=36 or mental age of >=18 months Parent/caregiver willingness to accompany child to clinic and monitor for side effects Exclusion Criteria: Unstable Seizure Disorder Psychoactive medication in the process of adjustment Antipsychotic medication in previous 3 months before baseline Systemic corticoids (inhalers allowed) Planned beginning of major behavioral intervention in 3 months of study or the 2 months prior to the study.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Mecamylamine<br>There will be 12 children in this arm. These children will receive the active medication (mecamylamine). | Drug: mecamylamine<br>* The dosage is titrated at 6 weeks of .5mg, 2 weeks of 2.5 mg, and 6 weeks of 5.0 mg. One pill is taken once daily.<br>* Other names: Inversine;|
| Placebo Comparator: Placebo<br>There will be 8 children in this arm. These children will receive placebo instead of the active medication. | Drug: placebo<br>* One pill is taken once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary measure will be a global composite derived by calculating the z scores on each measure other than CGI from published norms (or from the baseline descriptives, then averaging the z scores of the various outcome measures for each individual. |  | Baseline, weeks 2, 4, 6, 8, 10,12, and 14. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OSU Autism Rating Scale-DSM-IV |  | Baseline, week 6, 8, and 14. | 
| Repetitive Behavior Questionnaire |  | Baseline, week 2, 4, 6, 8, 10, 12, and 14 | 
| Aberrant Behavior Checklist |  | Baseline, week 2, 4, 6, 8, 10, 12, and 14. | 
| Ohio Autism Clinical Impressions Scale |  | Baseline, weeks 1, 2, 4, 6, 7, 8, 9, 10, 12, and 14. | 
| Social Responsiveness Scale |  | Baseline, weeks 2, 4, 6, 8, 10, 12, and 14. | 
| Expressive Vocabulary test-Second Edition |  | Baseline and week 14 | 
| Adverse Experience checklist and AE log |  | Baseline, weeks 1, 2, 4, 6, 7, 8, 9, 10, 12, and 14. | 
| Cognitive Battery |  | baseline, weeks 6, 8, and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autistic Disorder, Autism, Mecamylamine, Pervasive Developmental Disorder-Not Otherwise Specified