Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia (COATS)
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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 |
- 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.
- 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 |
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| 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 | |
| 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 May 23, 2013