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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
David C. Henderson, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00345033
First received: June 23, 2006
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Insulin Resistance
Drug: Aripiprazole
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Aripiprazole for Clozapine Associated Medical Morbidity

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in Total Cholesterol [ Time Frame: Measured at Baseline and Week 8 ] [ Designated as safety issue: Yes ]
    A comparison of aripiprazole group and placebo group in change in total cholesterol measured at Baseline and Week 8.

  • Change in Weight [ Time Frame: Measured at Baseline and Week 8 ] [ Designated as safety issue: Yes ]
    A comparison between aripiprazole group and placebo group in change in weight measured at Baseline and Week 8.

  • Change in Body Mass Index (BMI) [ Time Frame: Measured at Baseline and Week 8 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Measured at Baseline and Week 8 ] [ Designated as safety issue: Yes ]
    A comparison between the aripiprazole group and placebo group in change in glucose metabolism measured at Baseline and Week 8.

  • Change in Triglycerides [ Time Frame: Measured at Baseline and Week 8 ] [ Designated as safety issue: Yes ]
  • Change in Insulin Resistance [ Time Frame: Measured at Baseline and Week 8 ] [ Designated as safety issue: Yes ]
    A comparison between aripiprazole group and placebo group of change in insulin resistance measured at Baseline and Week 8.


Enrollment: 38
Study Start Date: March 2005
Study Completion Date: October 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will take aripiprazole 15mg/day for 8 weeks.
Drug: Aripiprazole
15-mg dose once a day for 8 weeks
Placebo Comparator: 2
Participants will take placebo for 8 weeks.
Drug: Placebo
1 tablet placebo dose once a day for 8 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00345033

Locations
United States, Massachusetts
Massachusetts General Hospital Schizophrenia Program
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: David C. Henderson, MD Massachusetts General Hospital
  More Information

Publications:

Responsible Party: David C. Henderson, Associate Professor of Psychiatry, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00345033     History of Changes
Other Study ID Numbers: R01 MH072635, R01MH072635, DSIR 83-ATAP
Study First Received: June 23, 2006
Results First Received: April 26, 2012
Last Updated: June 10, 2014
Health Authority: United States: Federal Government

Keywords provided by Massachusetts General Hospital:
Glucose Metabolism

Additional relevant MeSH terms:
Insulin Resistance
Schizophrenia
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clozapine
Aripiprazole
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents

ClinicalTrials.gov processed this record on July 20, 2014