Effectiveness of Aripiprazole for Improving Side Effects of Clozapine in the Treatment of People With Schizophrenia

Phase 4

Completed

Conditions: Schizophrenia
Insulin Resistance

Interventions: Drug: Aripiprazole
Drug: Placebo

Registration Number: NCT00345033

Lead Sponsor: Massachusetts General Hospital

Brief Summary: This study will evaluate the effects of combination treatment with aripiprazole and clozapine on insulin resistance, blood fat levels, and weight gain in people diagnosed with schizophrenia.

Detailed Description: Schizophrenia is a severely disabling brain disorder. People with schizophrenia often experience hallucinations and delusions, as well as overall difficulty with everyday functioning. Although the medications available to treat the disorder are generally effective, many cause undesirable side effects. Clozapine, for example, is a strong tranquilizer that functions like an antipsychotic medication. It has been shown to be effective in reducing the symptoms of schizophrenia, but can bring about serious side effects, including heart failure, weight gain, and diabetes. Aripiprazole, an atypical antipsychotic medication, has been shown to have fewer side effects than older antipsychotic drugs. The addition of aripiprazole to a clozapine treatment regimen may reduce the negative side effects of clozapine. This study will evaluate the effects of combination treatment with aripiprazole and clozapine on insulin resistance, blood fat levels, and weight gain in people with schizophrenia.

Individuals interested in participating in this 8-week, double-blind study will first attend a screening session at the study site. Medical and psychiatric evaluations will be completed, blood samples will be taken, and an EKG will be performed. Eligible participants will undergo baseline assessments and then be randomly assigned to receive either aripiprazole or placebo in addition to their prescribed dose of clozapine. Participants will take one 15-mg capsule of their assigned medication once a day for 8 weeks. Study visits will occur biweekly for the first 8 weeks, followed by one final follow-up visit at Week 12. At each study visit, medication will be distributed, and the following criteria will be assessed: vital signs; weight; complete blood count; medication side effects; and extrapyramidal symptoms (EPS), which are potential neurological side effects of antipsychotic medications and may include involuntary movements, tremors, and rigidity. The Week 8 visit will include an EKG, and assessments of the following criteria: vital signs; medication side effects; treatment efficacy; blood counts; weight and height; and waist and hip circumference. At baseline and Week 8, participants will also undergo a frequently sampled intravenous glucose tolerance test (FSIVGTT). This involves intravenous infusion of glucose followed by frequent blood sampling to measure insulin and glucose concentrations. During the 4 days prior to each FSIVGTT, participants will record their food intake and wear an activity monitor.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Diagnosis of schizophrenia (any subtype) or schizoaffective disorder (any subtype)
Treatment with clozapine for at least 1 year
Stable dose of clozapine for at least 1 month
Well established compliance with outpatient medications
Female participants of non-childbearing potential or of childbearing potential and willing to practice appropriate birth control methods (complete abstinence from sexual intercourse, female sterilization, sterilization of male partner, implants of levonorgestrel, injectable progestogen, oral contraceptives, intrauterine devices, or double barrier methods of contraception using spermicide with either a condom or diaphragm) during the study

Exclusion Criteria

Current substance abuse
Psychiatrically unstable
Significant medical illness, including severe cardiovascular, hepatic, or renal disease
History of immunosuppression
Current or recent radiation or chemotherapy treatment for cancer
Chronic use of steroids
Pregnant or breastfeeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Aripiprazole	Participants will take aripiprazole 15mg/day for 8 weeks.
2	Placebo	Participants will take placebo for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Triglycerides	Measured at Baseline and Week 8
Change in Total Cholesterol	Measured at Baseline and Week 8	A comparison of aripiprazole group and placebo group in change in total cholesterol measured at Baseline and Week 8.
Change in Weight	Measured at Baseline and Week 8	A comparison between aripiprazole group and placebo group in change in weight measured at Baseline and Week 8.
Change in Body Mass Index (BMI)	Measured at Baseline and Week 8	A comparison between aripiprazole group and placebo group of change in Body Mass Index (BMI) measured at Baseline and Week 8.
Change in Glucose Metabolism	Measured at Baseline and Week 8	A comparison between the aripiprazole group and placebo group in change in glucose metabolism measured at Baseline and Week 8.
Change in Insulin Resistance	Measured at Baseline and Week 8	A comparison between aripiprazole group and placebo group of change in insulin resistance measured at Baseline and Week 8.