Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia

NCT ID: NCT00802100

Last Updated: 2013-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2009-10-31

Brief Summary

This study will compare the safety and effectiveness of three different antipsychotic medications, as well as the use of other medications to limit treatment side effects, in adults with schizophrenia.

Detailed Description

Schizophrenia is a chronic brain disease affecting approximately 1% of Americans. Antipsychotic medications can treat some of the most severe symptoms of schizophrenia, but they are not a cure, are often taken for long periods of time, and can have severe side effects. Other, secondary medications can provide relief from some of the most common severe side effects. This study will compare the safety and effectiveness of three different antipsychotic medications, as well as the use of additional medications to limit treatment side effects, in adults with schizophrenia.

Participation in this study will last 28 to 30 weeks and include 11 visits to a study clinic. Each visit will last 2 to 3 hours. The first 2 visits will include screening and baseline measurements. The screening visit will take place at study entry, and the baseline visit will take place 3 to 14 days later. Study visits will then occur 1, 2, and 4 weeks after the baseline visit, followed by monthly visits.

At the baseline visit participants will be randomly assigned to receive olanzapine, perphenazine, or aripiprazole for 28 weeks. Dosage for all three antipsychotic medications will start at low levels and be increased to full strength over 2 weeks. If participants are taking another antipsychotic when they enter the study, this 2-week period will also be used to slowly reduce and then end treatment with the non-study antipsychotic. Side effects to all three antipsychotics will be monitored, and, depending on the side effect, one of three different medications will be added to the treatment regimen. If increased cholesterol levels are experienced with any antipsychotic, simvastatin will be added; if weight gain is experienced, metformin will be added; if involuntary movements, inner restlessness, or muscle stiffness are experienced, benztropine will be added. Because of already known side effects, participants assigned to olanzapine or perphenazine will automatically add metformin or benztropine, respectively, to their regimens.

Starting on the third study visit, participants will also undergo a behavioral treatment aimed at reducing cardiovascular risk factors. This behavioral treatment will involve nine 20-minute sessions, with phone calls being made to participants between sessions.

During each study visit, assessments will be made of schizophrenia symptoms, side effects, adherence to medication regimen, vital signs, waist circumference, and weight. Participants will also complete a questionnaire on use of health care services and undergo instructions on exercise and eating right. On visits 1, 5, 7, and 11, blood will be drawn for standard lab tests. Additional measures at the screening visit will include questions about medical and psychiatric history, a urine test for drugs, and a questionnaire about physical and social activities.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Olanzapine

Participants will receive treatment with olanzapine and metformin, with the possible addition of simvastatin or benztropine, depending on side effects.

Group Type: EXPERIMENTAL

Olanzapine

Intervention Type: DRUG

Daily tablets of 10 to 30 mg

Metformin

Intervention Type: DRUG

Daily tablets of 850 to 2550 mg

Simvastatin

Intervention Type: DRUG

Daily tablets of 20 to 40 mg

Benztropine

Intervention Type: DRUG

Daily tablets of 1 to 2 mg

Perphenazine

Participants will receive treatment with perphenazine and benztropine, with the possible addition of simvastatin or metformin, depending on side effects.

Group Type: EXPERIMENTAL

Perphenazine

Intervention Type: DRUG

Daily tablets of 8 to 24 mg

Metformin

Intervention Type: DRUG

Daily tablets of 850 to 2550 mg

Simvastatin

Intervention Type: DRUG

Daily tablets of 20 to 40 mg

Benztropine

Intervention Type: DRUG

Daily tablets of 1 to 2 mg

Aripiprazole

Participants will receive treatment with aripiprazole, with the possible addition of simvastatin, metformin, or benztropine, depending on side effects.

Group Type: EXPERIMENTAL

Aripiprazole

Intervention Type: DRUG

Daily tablets of 10 to 30 mg

Metformin

Intervention Type: DRUG

Daily tablets of 850 to 2550 mg

Simvastatin

Intervention Type: DRUG

Daily tablets of 20 to 40 mg

Benztropine

Intervention Type: DRUG

Daily tablets of 1 to 2 mg

Interventions

Olanzapine

Daily tablets of 10 to 30 mg

Intervention Type: DRUG

Perphenazine

Daily tablets of 8 to 24 mg

Intervention Type: DRUG

Aripiprazole

Daily tablets of 10 to 30 mg

Intervention Type: DRUG

Metformin

Daily tablets of 850 to 2550 mg

Intervention Type: DRUG

Simvastatin

Daily tablets of 20 to 40 mg

Intervention Type: DRUG

Benztropine

Daily tablets of 1 to 2 mg

Intervention Type: DRUG

Other Intervention Names

Zyprexa; Trilafon; Abilify; Glucophage; Zocor; Cogentin

Eligibility Criteria

Inclusion Criteria

• Diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID)
• Treated with antipsychotic medication for less than 5 years
• Adequate decisional capacity to make a choice about participating in this research study. Adequate decisional capacity will be determined through the aid of a 10-item decisional capacity quiz adapted from the University of California, San Diego, Brief Assessment of Capacity to Consent (UBACC) scale.
• Psychotic exacerbation within the month prior to study entry that required psychiatric hospitalization or an increased level of care
• Willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study. Acceptable methods include oral, injectable, or implanted contraceptives; intrauterine devices; or barrier methods, such as condoms, diaphragm, and spermicides.

Exclusion Criteria

• Body mass index at or above 35 kg/m2 or below 18 kg/m2
• Hemoglobin A1c level at or above 7%
• Hematocrit level at or above 31%
• Non-high density lipoprotein cholesterol at or above 190 mg/dL
• Triglycerides at or above 500 mg/dL
• Documented failure, defined as inefficacy or intolerability, with an adequate trial of olanzapine, perphenazine, or aripiprazole. Adequate trials last at least 4 weeks at a minimum dose of 15 mg/day of aripiprazole, 15 mg/day of olanzapine, or 16 mg/day of perphenazine.
• Current treatment with olanzapine, perphenazine, or aripiprazole for more than 1 month
• Known hypersensitivity to metformin, simvastatin, or benztropine
• Treatment with a medication prescribed for weight loss
• Diagnosis of diabetes mellitus or treatment with insulin or other diabetes medication
• Contraindications to metformin use, including any of the following:

• Diagnosis of congestive heart failure
• Renal impairment, defined as serum creatinine at or above 1.5 in males and 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits
• Hepatic disease, defined as aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) more than 1.5 times upper limit of normal (ULN) or total bilirubin more than 1.2 times ULN
• Metabolic acidosis, defined as a serum CO2 level less than the lower limit of normal
• Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material
• Alcohol abuse or dependence, as determined by SCID within the past month
• Concurrent treatment with certain drugs known to increase metformin blood levels
• Any unstable or serious medical condition, as judged by the investigator
• Pregnant or breastfeeding
• Diagnosis of mental retardation or delirium, as defined by the DSM-IV-TR

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marvin Swartz, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

T. Scott Stroup, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Joseph P. McEvoy, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

SHANTI Clinical Trials

Colton, California, United States

Stanford University

Palo Alto, California, United States

Yale University

New Haven, Connecticut, United States

University of Miami School of Medicine

Miami, Florida, United States

Medical College of Georgia

Augusta, Georgia, United States

Clinical Insights

Glen Burnie, Maryland, United States

University of Massachusetts

Worcester, Massachusetts, United States

Wayne State University

Detroit, Michigan, United States

University of Minnesota School of Medicine

Minneapolis, Minnesota, United States

Research Foundation for Mental Hygiene

New York, New York, United States

Duke University Medical Center-John Umstead Hospital

Butner, North Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

N01MH90001

Identifier Type: NIH

Identifier Source: secondary_id

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N01MH090001

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01 MH090001-02

Identifier Type: -

Identifier Source: org_study_id