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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:
NCT00802100
First received: December 3, 2008
Last updated: January 3, 2013
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Olanzapine
Drug: Perphenazine
Drug: Aripiprazole
Drug: Metformin
Drug: Simvastatin
Drug: Benztropine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of Optimal Antipsychotic Treatments for Schizophrenia Pilot Study

Resource links provided by NLM:


Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:
  • Feasibility of Randomizing a Cohort of Participants Meeting the Inclusion and Exclusion Criteria of the Study [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Goal was to randomize 60 participants who met eligibility criteria.


Secondary Outcome Measures:
  • Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment [ Time Frame: Measured over 28 weeks of study visits ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: December 2008
Study Completion Date: October 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Zyprexa
Drug: Metformin
Daily tablets of 850 to 2550 mg
Other Name: Glucophage
Drug: Simvastatin
Daily tablets of 20 to 40 mg
Other Name: Zocor
Drug: Benztropine
Daily tablets of 1 to 2 mg
Other Name: Cogentin
Experimental: Perphenazine
Participants will receive treatment with perphenazine and benztropine, with the possible addition of simvastatin or metformin, depending on side effects.
Drug: Perphenazine
Daily tablets of 8 to 24 mg
Other Name: Trilafon
Drug: Metformin
Daily tablets of 850 to 2550 mg
Other Name: Glucophage
Drug: Simvastatin
Daily tablets of 20 to 40 mg
Other Name: Zocor
Drug: Benztropine
Daily tablets of 1 to 2 mg
Other Name: Cogentin
Experimental: Aripiprazole
Participants will receive treatment with aripiprazole, with the possible addition of simvastatin, metformin, or benztropine, depending on side effects.
Drug: Aripiprazole
Daily tablets of 10 to 30 mg
Other Name: Abilify
Drug: Metformin
Daily tablets of 850 to 2550 mg
Other Name: Glucophage
Drug: Simvastatin
Daily tablets of 20 to 40 mg
Other Name: Zocor
Drug: Benztropine
Daily tablets of 1 to 2 mg
Other Name: Cogentin

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00802100

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

No publications provided

Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00802100     History of Changes
Other Study ID Numbers: N01 MH090001-02, N01MH90001
Study First Received: December 3, 2008
Results First Received: November 19, 2012
Last Updated: January 3, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):
Schizoaffective Disorder

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Benztropine
Olanzapine
Perphenazine
Aripiprazole
Metformin
Antipsychotic Agents
Simvastatin
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Uptake Inhibitors
Hypoglycemic Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on August 18, 2014