Clinical trial NCT00617240: Strategies to Reduce Antipsychotic-Associated Weight Gain in Youth
Official title: Metformin Mitigation of Atypical Antipsychotic-Induced Metabolic Dysregulation in Adolescent Youth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Weight Gain
Keywords: antipsychotic
metformin
children
adolescents
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Foundation of Hope, North Carolina
First posted: 2008-02-15
Enrollment: 9
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline to Week 24 in Body Mass Index (BMI)
timeFrame: 0-24 weeks
measure: Change From Baseline to Week 24 in Weight
timeFrame: 24 weeks
measure: Change From Baseline to Week 24 in Fat Mass
timeFrame: 24 weeks
Secondary outcomes:
measure: Change From Baseline to Week 24 in Insulin Level
timeFrame: 24 weeks
measure: Change From Baseline to Week 24 in Cholesterol Level
timeFrame: 24 weeks
measure: Change From Baseline to Week 24 in Triglycerides
timeFrame: 24 weeks
measure: Incidence of Metabolic Syndrome
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina, Department of Psychiatry
state: North Carolina
Study officials:
affiliation: Unversity of North Carolina, Department of Psychiatry
name: Linmarie Sikich, MD
role: PRINCIPAL_INVESTIGATOR
References: