Strategies to Reduce Antipsychotic-Associated Weight Gain in Youth

Phase 2

Completed

Brief Summary: 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.

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
1	metformin	metformin in doses from 250mg to 2000mg/day for 26 weeks
2	placebo	Matched placebo to metformin, doses between 250/0mg and 2000/0mg per day

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 24 in Body Mass Index (BMI)	0-24 weeks	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.
Change From Baseline to Week 24 in Weight	24 weeks	Change in weight is calculated as 24 weeks weight minus the baseline weight.
Change From Baseline to Week 24 in Fat Mass	24 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 24 in Insulin Level	24 weeks	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.
Change From Baseline to Week 24 in Cholesterol Level	24 weeks	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.
Change From Baseline to Week 24 in Triglycerides	24 weeks	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.
Incidence of Metabolic Syndrome	24 weeks	Metabolic syndrome is a combination of the medical disorders that, when co-occurring, increase the risk of developing cardiovascular disease and diabetes.