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

NCT ID: NCT01825798

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2015-10-31

Brief Summary

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

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.

Conditions

Overweight; Autism Spectrum Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Hydrochloride Oral Solution

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Metformin

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Riomet

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: collaborator

University of Pittsburgh Medical Center

OTHER

Sponsor Role: collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: collaborator

Holland Bloorview Kids Rehabilitation Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evdokia Anagnostou, M.D.

Role: PRINCIPAL_INVESTIGATOR

Holland Bloorview Kids Rehabilitation Hospital

Jeremey Veenstra-VanderWeele, M.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Benjamin Handen, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medical Center

Michael Aman, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Ohio State University/Nationwide Children's Hospital

Eric Butter, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Kevin Sanders, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Ohio State University/Nationwide Children's Hospital

Columbus, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 28942807 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27556593 (View on PubMed)

Other Identifiers

MET-10-2012

Identifier Type: -

Identifier Source: org_study_id