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

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.

Inclusion Criteria:

1. 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.

2. Minimum of 1 month on a stable atypical antipsychotic dose with no plans to change the
dose for the next 4 months.

3. 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).

4. Age 6 years to 17 years, 4 months.

5. 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.

6. 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:

1. History of intolerable adverse effects with metformin.

2. Prior history of an exposure to metformin of sufficient dose or duration to determine
response status.

3. 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.

4. Use of cationic drugs excreted by the kidneys.

5. Planned surgery or procedure requiring contrast.

6. Pregnant at screening contact.

7. On other psychotropic concomitant medications for less than 2 months.

8. 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.

9. Unable to tolerate blood work.

10. Current use of medication for target symptoms of appetite or weight loss.

11. Planned change of medication, medication dose, or behavioral treatment targeting
weight loss during the study period.