Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether metformin is safe and effective in the treatment of weight or weight gain in young people with Autism Spectrum Disorders (ASD) who are currently taking atypical antipsychotic medication.

Detailed Description
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This is a double-blind, placebo-controlled, multi-site randomized trial to evaluate oral fixed dose metformin (Riomet®) in decreasing weight or weight gain in children ages 6-17 years, 4 months with ASD who are currently taking atypical antipsychotic medication. A 16-week, double-blind, placebo-controlled randomized trial of metformin with dose guided by age will be conducted. A secondary study aim will be to assess the long-term safety and efficacy of metformin by conducting a 16-week open label continuation.

Official Title
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Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)

Conditions
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Overweight, Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Autism Spectrum Disorder (autistic disorder, pervasive developmental disorder not otherwise specified), Asperger's disorder) based upon an Autism Diagnostic Observation Scale (ADOS) and Diagnostic and Statistical Manual (DSM-IV) interview. Minimum of 1 month on a stable atypical antipsychotic dose with no plans to change the dose for the next 4 months. A documented greater than/equal to 7% increase in BMI since starting atypical antipsychotic therapy(going back as far as prior 12 months); or, if BMI is greater or equal to 85th percentile corrected for age and sex, then a greater than 5% body weight increase per year (prorated at greater than 5% body weight increase if medicated for longer than a year). Age 6 years to 17 years, 4 months. Subjects and their parents (guardians) must be judged reliable for medication compliance and must agree to keep appointments for study visits and tests as outlined in the protocol. Prior to the conduct of any study-specific procedures, the subject must provide assent to participate in the study (if developmentally appropriate), and their parents (guardians) must provide written informed consent. Exclusion Criteria: History of intolerable adverse effects with metformin. Prior history of an exposure to metformin of sufficient dose or duration to determine response status. History of liver disease, renal impairment, congestive heart failure, pernicious anemia, any other condition increasing the risk for lactic acidosis, or any serious medical illness requiring treatment. Use of cationic drugs excreted by the kidneys. Planned surgery or procedure requiring contrast. Pregnant at screening contact. On other psychotropic concomitant medications for less than 2 months. Treatment or planned treatment with concomitant medications with unacceptable interactions with metformin, including topiramate, levetiracetam, beta blockers, angiotensin-converting-enzyme (ACE) inhibitors, diuretics, or histamine H2 receptor antagonists. Unable to tolerate blood work. Current use of medication for target symptoms of appetite or weight loss. Planned change of medication, medication dose, or behavioral treatment targeting weight loss during the study period.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Hydrochloride Oral Solution<br> | Drug: Placebo<br>* The placebo hydrochloride oral solution will be prepared to match the appearance, smell and taste of the metformin as closely as possible. For children from 6-9 years of age, placebo will be started at 250 mg at their evening meal for 1 week, followed by the addition of a 250 mg dose at breakfast for 1 week. At the Week 2 visit, if placebo is well-tolerated, the dose will be increased to 500 mg twice daily. For children from 10-17 years of age, placebo will be started at 250 mg at their evening meal for 1 week, followed by the addition of a 250 mg dose at breakfast for 1 week. At the Week 2 visit, if placebo is well-tolerated, the dose will be increased to 500 mg twice daily. At the Week 4 visit, if placebo is well-tolerated, the dose will be increased to 850 mg twice daily.<br>|
| Experimental: Metformin<br> | Drug: Metformin<br>* Metformin will be dispensed in a liquid suspension of 100 mg/mL. For children 6-9 years of age, metformin will be started at 250 mg at their evening meal for 1 week, followed by the addition of a 250 mg dose at breakfast for 1 week. At the Week 2 visit, if metformin is well-tolerated, the dose will be increased to 500 mg twice daily. For children from 10-17 years of age, metformin will be started at 250 mg at their evening meal for 1 week, followed by the addition of a 250 mg dose at breakfast for 1 week. At the Week 2 visit, if metformin is well-tolerated, the dose will be increased to 500 mg twice daily. At the Week 4 visit, if metformin is well-tolerated, the dose will be increased to 850 mg twice daily.<br>* Other names: Riomet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Mass Index Z-score |  | Baseline, 16 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Additional Body Composition Parameters (Absolute Change in Weight) |  | Baseline, 16 Weeks | 
| Changes in Additional Body Composition Parameters (Relative Change in Weight) |  | Baseline, 16 Weeks | 
| Changes in Additional Body Composition Parameters (Absolute BMI) |  | Baseline, 16 Weeks | 
| Changes in Additional Body Composition Parameters (Abdominal Circumference) |  | Baseline, 16 Weeks | 
| Changes in Additional Body Composition Parameters (Hip Circumference) |  | Baseline, 16 Weeks | 
| Changes in Fasting Metabolic Parameters (Total Cholesterol) |  | Baseline, 16 Weeks | 
| Changes in Fasting Metabolic Parameters (LDL) |  | Baseline, 16 Weeks | 
| Changes in Fasting Metabolic Parameters (HDL) |  | Baseline, 16 Weeks | 
| Changes in Fasting Metabolic Parameters (Triglycerides) |  | Baseline, 16 Weeks | 
| Changes in Fasting Metabolic Parameters (Glucose) |  | Baseline, 16 Weeks | 
| Changes in Fasting Metabolic Parameters (Insulin) |  | Baseline, 16 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Overweight, Atypical Antipsychotic, Medication, Randomized Clinical Trial, Children