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

Schizophrenia Clinical Trial

Official title:

Aripiprazole for Clozapine Associated Medical Morbidity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00345033
• Other study ID #: R01MH072635
• Secondary ID: R01MH072635DSIR
• Status: Completed
• Phase: Phase 4
• First received: June 23, 2006
• Last updated: June 10, 2014
• Start date: March 2005
• Est. completion date: October 2010

Study information

• Verified date: June 2014
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: October 2010
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insulin Resistance
• Schizophrenia

Intervention

Drug:
• Aripiprazole
15-mg dose once a day for 8 weeks
• Placebo
1 tablet placebo dose once a day for 8 weeks

Locations

Country	Name	City	State
United States	Massachusetts General Hospital Schizophrenia Program	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (7)

Casey DE, Carson WH, Saha AR, Liebeskind A, Ali MW, Jody D, Ingenito GG; Aripiprazole Study Group. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology (Berl). 2003 Apr;166(4):391-9. Epub 2003 Feb 28. — View Citation

Goldstein LE, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey GK, Sachs G, Stern TA. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics. 1999 Sep-Oct;40(5):438-43. — View Citation

Hadigan C, Miller K, Corcoran C, Anderson E, Basgoz N, Grinspoon S. Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 1999 Jun;84(6):1932-7. — View Citation

Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81. — View Citation

Marder SR, McQuade RD, Stock E, Kaplita S, Marcus R, Safferman AZ, Saha A, Ali M, Iwamoto T. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res. 2003 Jun 1;61(2-3):123-36. — View Citation

Visser M, Fuerst T, Lang T, Salamone L, Harris TB. Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. Health, Aging, and Body Composition Study--Dual-Energy X-ray Absorptiometry and Body Composition Working Group. J Appl Physiol (1985). 1999 Oct;87(4):1513-20. — View Citation

Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002 Oct;63(10):856-65. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	Change in Triglycerides		Measured at Baseline and Week 8	Yes
Primary	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	Yes