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

NCT00345033 | Completed Phase 4 Results DMC

• 2 other identifiers: R01MH072635DSIR 83-ATAP
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Insulin Resistance

Keywords

Glucose Metabolism

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (2)

1

EXPERIMENTAL

Participants will take aripiprazole 15mg/day for 8 weeks.

Drug: Aripiprazole

2

PLACEBO COMPARATOR

Participants will take placebo for 8 weeks.

Drug: Placebo

Interventions

Aripiprazole DRUG

15-mg dose once a day for 8 weeks

1

Placebo DRUG

1 tablet placebo dose once a day for 8 weeks

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Massachusetts General Hospital Schizophrenia Program

Boston, Massachusetts, 02114, United States

Location

Related 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. doi: 10.1007/s00213-002-1344-3. Epub 2003 Feb 28.

  PMID: 12610718 BACKGROUND

• 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. doi: 10.1016/S0033-3182(99)71210-7. No abstract available.

  PMID: 10479950 BACKGROUND

• 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. doi: 10.1210/jcem.84.6.5738.

  PMID: 10372689 BACKGROUND

• 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. doi: 10.1176/appi.ajp.157.6.975.

  PMID: 10831479 BACKGROUND

• 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. doi: 10.1016/s0920-9964(03)00050-1.

  PMID: 12729864 BACKGROUND

• 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. doi: 10.1152/jappl.1999.87.4.1513.

  PMID: 10517786 BACKGROUND

• 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. doi: 10.4088/jcp.v63n1002.

  PMID: 12416594 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Insulin Resistance

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The limitations of this study include the relatively small sample size, short intervention period (8 weeks) and the lack of generalizability of our findings to patients with schizophrenia treated by antipsychotic agents other than clozapine.

Results Point of Contact

• Title: David C. Henderson
• Organization: Massachusetts General Hospital

dchenderson@partners.org

(617) 912-7800

Study Officials

• David C. Henderson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: June 23, 2006
• First Posted: June 27, 2006
• Study Start: March 1, 2005
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2010
• Last Updated: June 23, 2014
• Results First Posted: September 13, 2012

Record last verified: 2014-06

Locations

US (1)