Clinical trial NCT00802100: Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia
Official title: Comparison of Optimal Antipsychotic Treatments for Schizophrenia Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Keywords: Schizoaffective Disorder
Lead sponsor: National Institute of Mental Health (NIMH)
Sponsor class: NIH
First posted: 2008-12-04
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Feasibility of Randomizing a Cohort of Participants Meeting the Inclusion and Exclusion Criteria of the Study
timeFrame: Baseline
Secondary outcomes:
measure: Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment
timeFrame: Measured over 28 weeks of study visits
Other outcomes:
Locations:
city: Colton
country: United States
facility: SHANTI Clinical Trials
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Glen Burnie
country: United States
facility: Clinical Insights
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota School of Medicine
state: Minnesota
city: New York
country: United States
facility: Research Foundation for Mental Hygiene
state: New York
city: Butner
country: United States
facility: Duke University Medical Center-John Umstead Hospital
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Duke University
name: Marvin Swartz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: T. Scott Stroup, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Joseph P. McEvoy, MD
role: PRINCIPAL_INVESTIGATOR
References: