Strategies to Reduce Antipsychotic-Associated Weight Gain in Youth (PREVENT)

Metformin Mitigation of Atypical Antipsychotic-Induced Metabolic Dysregulation in Adolescent Youth

The purpose of this pilot study is to determine whether starting metformin in conjunction with a second-generation antipsychotic (SGA) and providing information about healthy eating and activity will prevent or reduce the amount of weight gain and the metabolic changes in adolescent youth typically seen with second-generation antipsychotic medication.

Study Overview

• Status: Completed
• Conditions: Weight Gain
• Intervention / Treatment: Drug: metformin; Drug: placebo

Detailed Description

This is a 24 week, placebo-controlled, random assignment pilot study in which participants will be randomized in a 1:1 ratio to receive either flexible-dose treatment with metformin for 6 months as well as a newly initiated second generation antipsychotic medication or to receive placebo and the newly initiated antipsychotic medication. All subjects will also be provided healthy lifestyle instruction. The study involves monthly visits for the duration of the study. Participants may be treated as inpatients or outpatients throughout the course of the study. Participants will receive a psychiatric evaluation, physical exam, lab work, ECG, medication treatment, and psychiatric care.

The goal is to evaluate the safety and efficacy of means to prevent and treat weight gain and the associated endocrine, metabolic, and inflammatory changes caused by antipsychotic medications. Behavioral treatments to reduce weight gain and metabolic problems after weight gain has occurred have had little impact. Such interventions must be intensive and sustained over months, if not years to be effective. Although basic lifestyle instruction (diet and physical activity) should be the standard of care for all children and adolescents at risk for becoming overweight, pharmacologic interventions may be the best option for substantially augmenting behavioral approaches to weight management.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, Department of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects will be between the ages of 10 and 17, male or female, any race or ethnicity
• Any SPMI pediatric diagnosis that meets DSM-IV criteria and frequently is treated with a SGA- typically but not limited to psychotic, mood, pervasive developmental, oppositional defiant, and conduct disorders
• SGA-naïve or less than 2 weeks exposure to any SGA, except ziprasidone
• Legal guardian able and willing to give written informed consent
• If competent, subject able and willing to assent for their own participation

Exclusion Criteria:

• Previous trial of metformin
• Recommendation for treatment with clozapine or ziprasidone
• Current use of insulin or any oral hypoglycemic agent
• Current use of a medication known to mitigate weight gain - amantidine, histamine (H2) antagonists (cimetidine, ranitidine, nizatidine), topiramate, orlistat, sibutramine, stimulants (dextroamphetamine, methylphenidate)
• Any current or past diagnosis of an eating disorder
• Diabetes mellitus
• Current active thyroid (TSH >18 microIU/ml; T4 total >18 mcg/dl), hepatic (2 LFTs >4x upper limits of normal), renal (serum Creatinine >1.4 mg/dL in females and serum Creatinine >1.5 mg/dL in males), cardiac, gastrointestinal, or adrenal disease
• Current substance abuse/dependence within past 2 weeks; a positive urine tox screen at baseline in the absence of meeting criteria for abuse/dependence will not preclude enrollment.
• Pregnancy or breast feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; metformin in doses from 250mg to 2000mg/day for 26 weeks	Drug: metformin; 500mg tablets, 250mg to 2000mg/day, po, BID to TID, 26 weeks; Other Names: Glucophage
Placebo Comparator: 2; Matched placebo to metformin, doses between 250/0mg and 2000/0mg per day	Drug: placebo; 500/0mg tablets, 250-2000mg/day divided BID to TID, po, 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in Body Mass Index (BMI)	Change in BMI-Body Mass Index (BMI) is a measure of body fat based on height, weight,gender and chronological age. Change in BMI is calculated as 24 weeks BMI minus the baseline BMI.	0-24 weeks
Change From Baseline to Week 24 in Weight	Change in weight is calculated as 24 weeks weight minus the baseline weight.	24 weeks
Change From Baseline to Week 24 in Fat Mass	Fat mass is a measure of excess body fat. Change in Fat Mass is calculated as 24 weeks fat mass minus the baseline fat mass.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in Insulin Level	Insulin is a peptide hormone and regulates carbohydrate and fat metabolism in the body.Change in Insulin level is calculated as the 24 weeks insulin level minus the baseline insulin level.	24 weeks
Change From Baseline to Week 24 in Cholesterol Level	According to the lipid hypothesis, abnormal cholesterol levels are strongly associated with cardiovascular disease because these promote atherosclerosis.Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter(dL) of blood.Change in cholesterol levels is measured at 24 weeks minus the levels at baseline.	24 weeks
Change From Baseline to Week 24 in Triglycerides	In the human body, high levels of triglyceride fats in the bloodstream have been linked to atherosclerosis and, by extension, the risk of heart disease and stroke. A change in triglycerides is calculated from 24 weeks minus baseline levels.	24 weeks
Incidence of Metabolic Syndrome	Metabolic syndrome is a combination of the medical disorders that, when co-occurring, increase the risk of developing cardiovascular disease and diabetes.	24 weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Foundation of Hope, North Carolina
• Investigators: Principal Investigator: Linmarie Sikich, MD, Unversity of North Carolina, Department of Psychiatry

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 5, 2008
• First Submitted That Met QC Criteria: February 14, 2008
• First Posted (Estimate): February 15, 2008

Study Record Updates

• Last Update Posted (Estimate): March 11, 2014
• Last Update Submitted That Met QC Criteria: February 7, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: children; adolescents; metformin; antipsychotic
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 05-2992 GCRC-2501