Clinical trial NCT01825798: Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
Official title: Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Overweight
Autism Spectrum Disorder
Keywords: Metformin
Overweight
Atypical Antipsychotic
Medication
Randomized Clinical Trial
Children
Lead sponsor: Anagnostou, Evdokia, M.D.
Sponsor class: INDIV
Collaborators: name: Massachusetts General Hospital
name: Vanderbilt University
name: University of Pittsburgh
name: Nationwide Children's Hospital
name: Ohio State University
First posted: 2013-04-08
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Body Mass Index Z-score
timeFrame: Baseline, 16 Weeks
Secondary outcomes:
measure: Changes in Additional Body Composition Parameters (Absolute Change in Weight)
timeFrame: Baseline, 16 Weeks
measure: Changes in Additional Body Composition Parameters (Relative Change in Weight)
timeFrame: Baseline, 16 Weeks
measure: Changes in Additional Body Composition Parameters (Absolute BMI)
timeFrame: Baseline, 16 Weeks
measure: Changes in Additional Body Composition Parameters (Abdominal Circumference)
timeFrame: Baseline, 16 Weeks
measure: Changes in Additional Body Composition Parameters (Hip Circumference)
timeFrame: Baseline, 16 Weeks
measure: Changes in Fasting Metabolic Parameters (Total Cholesterol)
timeFrame: Baseline, 16 Weeks
measure: Changes in Fasting Metabolic Parameters (LDL)
timeFrame: Baseline, 16 Weeks
measure: Changes in Fasting Metabolic Parameters (HDL)
timeFrame: Baseline, 16 Weeks
measure: Changes in Fasting Metabolic Parameters (Triglycerides)
timeFrame: Baseline, 16 Weeks
measure: Changes in Fasting Metabolic Parameters (Glucose)
timeFrame: Baseline, 16 Weeks
measure: Changes in Fasting Metabolic Parameters (Insulin)
timeFrame: Baseline, 16 Weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University/Nationwide Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Toronto
country: Canada
facility: Holland Bloorview Kids Rehabilitation Hospital
state: Ontario
Study officials:
affiliation: Holland Bloorview Kids Rehabilitation Hospital
name: Evdokia Anagnostou, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Jeremey Veenstra-VanderWeele, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Medical Center
name: Benjamin Handen, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University/Nationwide Children's Hospital
name: Michael Aman, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nationwide Children's Hospital
name: Eric Butter, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: Kevin Sanders, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.