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

NCT01825798 | Completed Phase 3 Results DMC

• 1 other identifier: MET-10-2012
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 4

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.

Conditions

Overweight; Autism Spectrum Disorder

Keywords

Metformin; Overweight; Atypical Antipsychotic; Medication; Randomized Clinical Trial; Children

Outcome Measures

Primary Outcomes (1)

• Change in Body Mass Index Z-score

  Baseline, 16 Weeks

Secondary Outcomes (11)

• 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

Study Arms (2)

Placebo Hydrochloride Oral Solution

PLACEBO COMPARATOR

Drug: Placebo

Metformin

EXPERIMENTAL

Drug: Metformin

Interventions

Metformin 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.

Also known as: Riomet

Metformin

Placebo 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.

Placebo Hydrochloride Oral Solution

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Holland Bloorview Kids Rehabilitation Hospital: lead
• Massachusetts General Hospital: collaborator
• Vanderbilt University: collaborator
• University of Pittsburgh Medical Center: collaborator
• Nationwide Children's Hospital: collaborator
• Ohio State University: collaborator

Study Sites (4)

Ohio State University/Nationwide Children's Hospital

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15203, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, M4G 1R8, Canada

Location

Related Publications (2)

• 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.

  PMID: 28942807 DERIVED

• 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.

  PMID: 27556593 DERIVED

MeSH Terms

Conditions

Overweight; Autism Spectrum Disorder

Interventions

Metformin

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Treatment length doesn't capture metabolic benefits. Unable to evaluate maintenance of initial improvements. Limited information on length of overall exposure to antipsychotic medications. No evaluation on benefit of lifestyle.

Results Point of Contact

• Title: Dr. Evdokia Anagnostou
• Organization: Holland Bloorview Kids Rehabilition Hospital

eanagnostou@hollandbloorview.ca

416-753-6005

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2013
• First Posted: April 8, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 16, 2025
• Results First Posted: February 22, 2018

Record last verified: 2018-01

Locations

US (3); CA (1)