Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia (COATS)

Comparison of Optimal Antipsychotic Treatments for Schizophrenia Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Olanzapine; Drug: Metformin; Drug: Simvastatin; Drug: Benztropine; Drug: Perphenazine; Drug: Aripiprazole

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Colton, California, United States, 92324
      • Shanti Clinical Trials
    • Palo Alto, California, United States, 94305
      • Stanford University
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • Florida
    • Miami, Florida, United States, 33316
      • University of Miami School of Medicine
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Clinical Insights
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota School of Medicine
  • New York
    • New York, New York, United States, 10032
      • Research Foundation for Mental Hygiene
  • North Carolina
    • Butner, North Carolina, United States, 27509
      • Duke University Medical Center-John Umstead Hospital
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olanzapine; Participants will receive treatment with olanzapine and metformin, with the possible addition of simvastatin or benztropine, depending on side effects.	Drug: Olanzapine; Daily tablets of 10 to 30 mg; Other Names: Zyprexa; Drug: Metformin; Daily tablets of 850 to 2550 mg; Other Names: Glucophage; Drug: Simvastatin; Daily tablets of 20 to 40 mg; Other Names: Zocor; Drug: Benztropine; Daily tablets of 1 to 2 mg; Other Names: Cogentin
Experimental: Perphenazine; Participants will receive treatment with perphenazine and benztropine, with the possible addition of simvastatin or metformin, depending on side effects.	Drug: Metformin; Daily tablets of 850 to 2550 mg; Other Names: Glucophage; Drug: Simvastatin; Daily tablets of 20 to 40 mg; Other Names: Zocor; Drug: Benztropine; Daily tablets of 1 to 2 mg; Other Names: Cogentin; Drug: Perphenazine; Daily tablets of 8 to 24 mg; Other Names: Trilafon
Experimental: Aripiprazole; Participants will receive treatment with aripiprazole, with the possible addition of simvastatin, metformin, or benztropine, depending on side effects.	Drug: Metformin; Daily tablets of 850 to 2550 mg; Other Names: Glucophage; Drug: Simvastatin; Daily tablets of 20 to 40 mg; Other Names: Zocor; Drug: Benztropine; Daily tablets of 1 to 2 mg; Other Names: Cogentin; Drug: Aripiprazole; Daily tablets of 10 to 30 mg; Other Names: Abilify

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Randomizing a Cohort of Participants Meeting the Inclusion and Exclusion Criteria of the Study	Goal was to randomize 60 participants who met eligibility criteria.	Baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment	Measured over 28 weeks of study visits

Collaborators and Investigators

• Sponsor: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Marvin Swartz, MD, Duke University; Principal Investigator: T. Scott Stroup, MD, MPH, University of North Carolina, Chapel Hill; Principal Investigator: Joseph P. McEvoy, MD, Duke University

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: December 3, 2008
• First Submitted That Met QC Criteria: December 3, 2008
• First Posted (Estimate): December 4, 2008

Study Record Updates

• Last Update Posted (Estimate): February 8, 2013
• Last Update Submitted That Met QC Criteria: January 3, 2013
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Schizoaffective Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Antimetabolites; Antiemetics; Gastrointestinal Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Dopamine Uptake Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Olanzapine; Aripiprazole; Metformin; Simvastatin; Perphenazine; Benztropine
• Other Study ID Numbers: N01 MH090001-02; N01MH90001 (Other Grant/Funding Number: NIMH)