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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Aripiprazole for Clozapine Associated Medical Morbidity

Conditions
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Schizophrenia, Insulin Resistance

Intervention / Treatment
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* Drug: Aripiprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will take aripiprazole 15mg/day for 8 weeks. | Drug: Aripiprazole<br>* 15-mg dose once a day for 8 weeks<br>|
| Placebo Comparator: 2<br>Participants will take placebo for 8 weeks. | Drug: Placebo<br>* 1 tablet placebo dose once a day for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose Metabolism