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Trial record 1 of 1 for:    comparison of optimal antipsychotic treatments for adults with schizophrenia
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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

December 3, 2008
January 3, 2013
December 2008
September 2009   (final data collection date for primary outcome measure)
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.
  • Feasibility of randomizing a cohort of participants meeting the inclusion and exclusion criteria of the study [ Time Frame: Measured pre- and post-treatment ] [ Designated as safety issue: No ]
  • Identification of appropriate clinical sites to mount the proposed clinical trial [ Time Frame: Measured pre- and post-treatment ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Measured over 28 weeks of study visits ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00802100 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Schizophrenia
  • Drug: Olanzapine
    Daily tablets of 10 to 30 mg
    Other Name: Zyprexa
  • Drug: Perphenazine
    Daily tablets of 8 to 24 mg
    Other Name: Trilafon
  • 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
  • Experimental: Olanzapine
    Participants will receive treatment with olanzapine and metformin, with the possible addition of simvastatin or benztropine, depending on side effects.
    Interventions:
    • Drug: Olanzapine
    • Drug: Metformin
    • Drug: Simvastatin
    • Drug: Benztropine
  • Experimental: Perphenazine
    Participants will receive treatment with perphenazine and benztropine, with the possible addition of simvastatin or metformin, depending on side effects.
    Interventions:
    • Drug: Perphenazine
    • Drug: Metformin
    • Drug: Simvastatin
    • Drug: Benztropine
  • Experimental: Aripiprazole
    Participants will receive treatment with aripiprazole, with the possible addition of simvastatin, metformin, or benztropine, depending on side effects.
    Interventions:
    • Drug: Aripiprazole
    • Drug: Metformin
    • Drug: Simvastatin
    • Drug: Benztropine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
October 2009
September 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 40 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00802100
N01 MH090001-02, N01MH90001
Yes
National Institute of Mental Health (NIMH)
National Institute of Mental Health (NIMH)
Not Provided
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
National Institute of Mental Health (NIMH)
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP