Effects of Pravastatin on Cholesterol, Inflammation and Cognition in Schizophrenia

Phase 4

Completed

Conditions: Schizophrenia
Schizophreniform Disorders
Schizoaffective Disorders

Interventions: Drug: Pravastatin
Drug: Placebo

Registration Number: NCT01082588

Lead Sponsor: Massachusetts General Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
pravastatin	Pravastatin	pravastatin 40mg, once a day, shortly after baseline for 12 consecutive weeks
Placebo	Placebo	placebo, once a day, shortly after baseline for 12 consecutive weeks

Primary Outcome Measures

Name	Time	Method
Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12	Baseline, 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.
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	Baseline, 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.
Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12	Baseline, 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.
Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12	Baseline, 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.
Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12	Baseline, 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.