Effects of Pravastatin on Cholesterol, Inflammation and Cognition in Schizophrenia

Study Overview
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Brief Summary
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This study involves people with schizophrenia or schizoaffective disorder, who are currently taking antipsychotic medications. Some antipsychotic medications may cause an increase in cholesterol levels, which may lead to inflammation in the body. Inflammation poses a risk in developing heart disease, diabetes and problems with brain function. The purpose of this study is to see if pravastatin can: Lower cholesterol Decrease inflammation Improve cognition in patients with schizophrenia

Detailed Description
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This study is a 12-week randomized, double-blind, placebo-controlled pilot study of pravastatin 40mg a day, administered for 12 consecutive weeks to subjects with schizophrenia to examine pravastatin's effects on lowering cholesterol levels and inflammatory markers, and improving cognition. The study will be conducted at the Freedom Trail Clinic and will use the Massachusetts General Hospital Clinical Research Center. The innovative approach of using pravastatin to not only decrease cholesterol levels, but to decrease inflammation and improve cognition in patients with schizophrenia is promising and may lead to a different approach to treatment in this population.

Official Title
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Phase 4 Study of the Effects of Pravastatin on Cholesterol Levels, Inflammation and Cognition in Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorders, Schizophreniform Disorders

Intervention / Treatment
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* Drug: Pravastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age 18-68 years Diagnosis of schizophrenia, any subtype, schizoaffective disorder, any subtype or schizophreniform disorder Well established compliance with outpatient medications including their antipsychotic medication Exclusion Criteria: Inability to provide informed consent Current substance and alcohol abuse Significant medical illness, including congestive heart failure, severe cardiovascular disease, renal disease (serum creatinine > 1.5), severe hepatic impairment or active liver disease, anemia (hemoglobin <11.0 gm/dL), history of severe head injury, and not treated muscle disease. Psychiatrically unstable Women of child bearing potential who are pregnant, breastfeeding, or who are unwilling or unable to use an effective form of birth control during the entire study Subjects treated with anti-inflammatory drugs (including daily aspirin and ibuprofen), thiazide diuretics; agents that induce weight loss, and St. John's Wort will be excluded from the study Current history of untreated thyroid disease Current treatment with insulin Subjects being treated with drugs such as: colchicine, azole antifungals (fluconazole, ketoconazole, itraconazole); macrolide antibiotics (clarithromycin, erythromycin); HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir) that inhibit the CYP 450 3A liver enzyme Known hypersensitivity to pravastatin or any of its components

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pravastatin<br>pravastatin 40mg, once a day, shortly after baseline for 12 consecutive weeks | Drug: Pravastatin<br>* pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks<br>* Other names: Pravachol;|
| Placebo Comparator: Placebo<br>placebo, once a day, shortly after baseline for 12 consecutive weeks | Drug: Placebo<br>* pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LDL-cholesterol Between Baseline and Week 12 |  | Baseline, week 12 | 
| Change in C-Reactive Protein (CRP) From Baseline to Week 12 |  | Baseline, week 12 | 
| Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12 | The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery measures cognitive functioning within 7 domains: speed of processing, attention/vigilance, working memory (non verbal and verbal), verbal learning, visual learning, reasoning and problem solving and social cognition. The composite score is calculated by the MATRICS computer program, which equally weights each of the 7 domain scores. The range of composite scores is 20-80. Higher scores indicate higher levels or cognitive functioning, while lower scores indicate lower levels of cognitive functioning. | Baseline, week 12 | 
| Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12 | The Positive and Negative Syndrome Scale (PANSS) is a scale used to rate severity of schizophrenia. All items are summed to calculate the total score. The scale range is 30-210. Better outcomes have lower numbers and worse outcomes have higher numbers. | Baseline, week 12 | 
| Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12 | This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. | Baseline, week 12 | 
| Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12 | This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. | Baseline, week 12 | 
| Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12 | This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 15-105. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. | Baseline, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognition, schizophrenia, pravastatin, inflammation, antipsychotics, cholesterol