Clinical trial NCT00806234
Conditions: Psychotic Disorders
Keywords: Weight Gain Obesity IMPACT Antipsychotic Treatment Excessive Weight Gain Associated With Antipsychotic Treatment Hybrid Efficacy/Effectiveness Design Reducing Weight Gain Improving Metabolic Parameters Aripiprazole Metformin Risperdal Seroquel Quetiapine Olanzapine Zyprexa Geodon Risperidone Abilify Trilafon Perphenazine Glucophage Paliperidone Olanzapine/fluoxetine
Sponsor: Johns Hopkins University
Start date: 2009-01-01; Completion date: 2014-03-01
Enrollment: 127 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
This study will test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications.

Detailed description:
Disorders that involve severe dysregulation of mood or thoughts in children -- such as early onset bipolar spectrum (BPS) and schizophrenia spectrum (SS) disorders -- are commonly treated with antipsychotic medications. However, many of the newest and most commonly prescribed antipsychotic medications can cause weight gain and metabolic dysfunctions. Use of these newer antipsychotics, called second generation antipsychotics (SGAs), is increasing rapidly in children, and the risk of weight gain from SGAs is higher among children than adults. Excessive weight gain can lead to obesity, which, in turn, can lead to increased health care costs, increased risk of sickness, and lower life expectancy. These factors are enhanced in children and adolescents who grow up obese.

Two different strategies to reduce weight gain and metabolic side effects from SGAs will be tested in this study. The first strategy involves switching from the current SGA to a lower risk agent (aripiprazole or perphenazine) hypothesized to result in weight loss and improved metabolic functioning. The second strategy involves taking the medication metformin in addition to the current SGA. Metformin is approved by the Food and Drug Administration (FDA) to promote weight loss in youth with diabetes and has been effective in reducing weight in youth taking SGAs.

Participation in this study will last between 26 and 27 weeks and will be divided into two parts. The first part will last 2 to 3 weeks and include three study visits. During this part, participants will undergo a physical exam, an electrocardiogram (EKG), a dual energy X-ray absorptiometry (DXA) test, and blood tests. The DXA measures body fat.

The second part will last 24 weeks and include nine study visits. During this part, participants will be randomly assigned to one of three conditions: gradual switch of current SGA medication to either aripiprazole or perphenazine, addition of metformin to current SGA medication, or no change to treatment with current SGA medication. Visits will take place on Weeks 1, 2, 4, 6, 8, 12, 16, 20, and 24. At each visit, participants will meet with a study doctor who will assess symptoms and side effects, and participants and their guardians will receive information and recommendations about childhood obesity and weight loss. There will also be monthly urine pregnancy tests, and two blood tests.

Arms: arm 1: Participants will continue on current antipsychotic medication. arm 2: Participants will undergo a staggered switch from current antipsychotic medication to aripiprazole or perphenazine. arm 3: Participants will add metformin to current antipsychotic medication treatment.
Interventions: intervention 1: Aripiprazole or Perphenazine intervention 2: Metformin intervention 3: Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine
Intervention descriptions: intervention 1: Baseline second generation antipsychotic (SGA) treatment will be gradually decreased and discontinued over 8 weeks while treatment with aripiprazole or perphenazine will be increased to effective levels. intervention 2: Metformin treatment will be added to current SGA treatment, with dosing based on participant weight and increased according to a preset titration schedule unless side effects interfere. intervention 3: Current antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated

Protocol documents: