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

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.

Study Overview

• Status: Completed
• Conditions: Overweight; Autism Spectrum Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Metformin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 1R8
      • Holland Bloorview Kids Rehabilitation Hospital
• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University/Nationwide Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15203
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin	Drug: Metformin; 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.; Other Names: Riomet
Placebo Comparator: Placebo Hydrochloride Oral Solution	Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Holland Bloorview Kids Rehabilitation Hospital
• Collaborators: Massachusetts General Hospital; Vanderbilt University; Ohio State University; Nationwide Children's Hospital; University of Pittsburgh Medical Center
• Investigators: Principal Investigator: Evdokia Anagnostou, M.D., Holland Bloorview Kids Rehabilitation Hospital; Principal Investigator: Jeremey Veenstra-VanderWeele, M.D., Columbia University; Principal Investigator: Benjamin Handen, Ph.D., University of Pittsburgh Medical Center; Principal Investigator: Michael Aman, Ph.D., Ohio State University/Nationwide Children's Hospital; Principal Investigator: Eric Butter, Ph.D., Nationwide Children's Hospital; Principal Investigator: Kevin Sanders, M.D., Vanderbilt University

Publications and helpful links

General Publications

• Handen BL, Anagnostou E, Aman MG, Sanders KB, Chan J, Hollway JA, Brian J, Arnold LE, Capano L, Williams C, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Peleg N, Odrobina D, McAuliffe-Bellin S, Marler S, Wong T, Wagner A, Hadjiyannakis S, Macklin EA, Veenstra-VanderWeele J. A Randomized, Placebo-Controlled Trial of Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorder: Open-Label Extension. J Am Acad Child Adolesc Psychiatry. 2017 Oct;56(10):849-856.e6. doi: 10.1016/j.jaac.2017.07.790. Epub 2017 Aug 19.
• Anagnostou E, Aman MG, Handen BL, Sanders KB, Shui A, Hollway JA, Brian J, Arnold LE, Capano L, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Hadjiyannakis S, Peleg N, Odrobina D, McAuliffe-Bellin S, Zakroysky P, Marler S, Wagner A, Wong T, Macklin EA, Veenstra-VanderWeele J. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Sep 1;73(9):928-37. doi: 10.1001/jamapsychiatry.2016.1232.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: February 7, 2013
• First Submitted That Met QC Criteria: April 5, 2013
• First Posted (Estimated): April 8, 2013

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Children; Overweight; Metformin; Medication; Randomized Clinical Trial; Atypical Antipsychotic
• Additional Relevant MeSH Terms: Mental Disorders; Nutrition Disorders; Overnutrition; Body Weight; Neurodevelopmental Disorders; Autism Spectrum Disorder; Overweight; Autistic Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Hypoglycemic Agents; Metformin
• Other Study ID Numbers: MET-10-2012