Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia

Condition(s) targeted: Schizophrenia

Intervention: Olanzapine (Drug); Perphenazine (Drug); Aripiprazole (Drug); Behavioral Treatment (Behavioral); Metformin (Drug); Simvastatin (Drug); Benztropine (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute of Mental Health (NIMH)

Official(s) and/or principal investigator(s):
Marvin Swartz, MD, Principal Investigator, Affiliation: Duke University
T. Scott Stroup, MD, MPH, Principal Investigator, Affiliation: The University of North Carolina at Chapel Hill
Joseph P. McEvoy, MD, Principal Investigator, Affiliation: Duke University

Overall contact:
Ingrid A. Rojas, MPM, Phone: 919-843-7365, Email: irojas@med.unc.edu

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.

Official title: Comparison of Optimal Antipsychotic Treatments for Schizophrenia Pilot Study

Study design: Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Identification of appropriate clinical sites to mount the proposed clinical trial

Feasibility of randomizing a cohort of participants meeting the inclusion and exclusion criteria of the study

Feasibility of protocol implementation with a high level of protocol adherence and low participant attrition. The goal is for fewer than 25% of enrolled participants to be poorly adherent to the protocol interventions.

Secondary outcome: Antipsychotic efficacy, defined as completion of the trial without psychiatric hospitalization, clinician decision to discontinue treatment, or patient decision to discontinue treatment

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.

Minimum age: 18 Years. Maximum age: 40 Years. Gender(s): Both.

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

Ingrid A. Rojas, MPM, Phone: 919-843-7365, Email: irojas@med.unc.edu

SHANTI Clinical Trials, Colton, California 92324, United States; Recruiting
Satish Sood, PhD, Phone: 909-423-0367, Email: satishsood41@gmail.com
Gurmet S. Multani, MD, Principal Investigator

Stanford University, Palo Alto, California 94305, United States; Not yet recruiting
Alexandra Bond, Phone: 650-723-6678, Email: alexbond@stanford.edu
Ira Glick, MD, Principal Investigator

Yale University, New Haven, Connecticut 06519, United States; Not yet recruiting
Maegan Krasenics, Phone: 203-974-7544, Email: maegan.krasenics@yale.edu
Cyril D'Souza, MD, Principal Investigator

University of Miami School of Medicine, Miami, Florida 33316, United States; Recruiting
Karina Fajardo, MD, Phone: 305-355-8186, Email: compstar@med.miami.edu
Richard Steinbook, MD, Principal Investigator

Medical College of Georgia, Augusta, Georgia 30912, United States; Recruiting
Edna Stirewalt, Phone: 706-721-7968, Email: estirewalt@mcg.edu
Peter F. Buckley, MD, Principal Investigator

Clinical Insights, Glen Burnie, Maryland 21061, United States; Recruiting
Lorri Cerro, Phone: 410-768-2630, Email: cerro@clinicalinsights.com
Lawrence Adler, MD, Principal Investigator

University of Massachusetts, Worcester, Massachusetts 01605, United States; Recruiting
Chelsea York, Phone: 508-856-5312, Email: Chelsea.York@umassmed.edu
Jayendra Patel, MD, Principal Investigator

Wayne State University, Detroit, Michigan 48201, United States; Not yet recruiting
Vickie Wilson, Phone: 313-745-3585, Email: vwilson@med.wayne.edu
Rajaprabhakaran Rajarethinam, MD, Principal Investigator

University of Minnesota School of Medicine, Minneapolis, Minnesota 55454, United States; Recruiting
Elizabeth Lemke, Phone: 612-627-4840, Email: lemke022@umn.edu
Stephen Olson, MD, Principal Investigator

Research Foundation for Mental Hygiene, New York, New York 10032, United States; Not yet recruiting
Marlene Carlson, MPH, Phone: 212-543-5678, Email: mcarlson@pi.cpmc.columbia.edu
Jeffrey A. Lieberman, MD, Principal Investigator

Duke University Medical Center-John Umstead Hospital, Butner, North Carolina 27509, United States; Recruiting
Nancy McGrady, Phone: 919-575-7213, Email: nmcgrady@duke.edu
Joseph McEvoy, MD, Principal Investigator

University of Texas Southwestern Medical Center, Dallas, Texas 75235, United States; Recruiting
Mark Bushong, Phone: 214-648-4603, Email: mark.bushong@UTshouthwestern.edu
Matthew Byerly, MD, Principal Investigator

Baylor College of Medicine, Houston, Texas 77030, United States; Recruiting
Jessica Eiseman, Phone: 713-873-6136, Email: eiseman@bcm.tmc.edu
Michael Barber, MD, Principal Investigator

Rogers Center for Research and Training, Inc, Milwaukee, Wisconsin 53227-1133, United States; Not yet recruiting
Amy Perkins, Phone: 414-328-3702, Email: APerkins@rogershospital.org
Kambiz Pahlavan, MD, Principal Investigator

Starting date: December 2008
Ending date: September 2009
Last updated: February 11, 2009