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

June 23, 2006
June 10, 2014
March 2005
October 2009   (final data collection date for primary outcome measure)
  • 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.
  • Measured at Week 12: Fasting lipids, including triglycerides and total cholesterol
  • Body Mass Index (BMI)
  • Weight
  • Insulin resistance and glucose metabolism
  • Predictions for improvement in these outcomes
Complete list of historical versions of study NCT00345033 on ClinicalTrials.gov Archive Site
Not Provided
  • Measured at Week 12: Food intake
  • Energy expenditure
  • Systematic Assessment for Treatment Emergent Effects (SAFTEE)
  • Vital signs
  • Plasminogen activator molecule-1 (PAI-1)
  • LDL particle size
  • C-reactive protein
  • Soluble intercellular adhesion molecule-1
  • Lipid abnormalities
Not Provided
Not Provided
 
Effectiveness of Aripiprazole for Improving Side Effects of Clozapine in the Treatment of People With Schizophrenia
Aripiprazole for Clozapine Associated Medical Morbidity

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Insulin Resistance
  • Drug: Aripiprazole
    15-mg dose once a day for 8 weeks
  • Drug: Placebo
    1 tablet placebo dose once a day for 8 weeks
  • Experimental: 1
    Participants will take aripiprazole 15mg/day for 8 weeks.
    Intervention: Drug: Aripiprazole
  • Placebo Comparator: 2
    Participants will take placebo for 8 weeks.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
38
October 2010
October 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00345033
R01 MH072635, R01MH072635, DSIR 83-ATAP
Yes
David C. Henderson, Massachusetts General Hospital
Massachusetts General Hospital
National Institute of Mental Health (NIMH)
Principal Investigator: David C. Henderson, MD Massachusetts General Hospital
Massachusetts General Hospital
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP