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

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ClinicalTrials.gov Identifier: NCT00345033
Recruitment Status : Completed
First Posted : June 27, 2006
Results First Posted : September 13, 2012
Last Update Posted : June 23, 2014
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
David C. Henderson, 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.

Condition or disease Intervention/treatment Phase
Schizophrenia Insulin Resistance Drug: Aripiprazole Drug: Placebo Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Aripiprazole for Clozapine Associated Medical Morbidity
Study Start Date : March 2005
Actual Primary Completion Date : October 2009
Actual Study Completion Date : October 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Change in Total Cholesterol [ Time Frame: 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.

  2. Change in Weight [ Time Frame: Measured at Baseline and Week 8 ]
    A comparison between aripiprazole group and placebo group in change in weight measured at Baseline and Week 8.

  3. Change in Body Mass Index (BMI) [ Time Frame: 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.

  4. Change in Glucose Metabolism [ Time Frame: 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.

  5. Change in Triglycerides [ Time Frame: Measured at Baseline and Week 8 ]
  6. Change in Insulin Resistance [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00345033


Locations
United States, Massachusetts
Massachusetts General Hospital Schizophrenia Program
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: David C. Henderson, MD Massachusetts General Hospital

Publications:

Responsible Party: David C. Henderson, Associate Professor of Psychiatry, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00345033     History of Changes
Other Study ID Numbers: R01MH072635 ( U.S. NIH Grant/Contract )
R01MH072635 ( U.S. NIH Grant/Contract )
DSIR 83-ATAP
First Posted: June 27, 2006    Key Record Dates
Results First Posted: September 13, 2012
Last Update Posted: June 23, 2014
Last Verified: June 2014

Keywords provided by David C. Henderson, Massachusetts General Hospital:
Glucose Metabolism

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