Effects of Pravastatin on Cholesterol, Inflammation and Cognition in Schizophrenia

Condition(s) targeted: Schizophrenia; Schizoaffective Disorders; Schizophreniform Disorders

Intervention: Pravastatin (Drug); Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Massachusetts General Hospital

Official(s) and/or principal investigator(s):
David C Henderson, M.D., Principal Investigator, Affiliation: Massachusetts General Hospital

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

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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Change in LDL-cholesterol Between Baseline and Week 12

Change in C-Reactive Protein (CRP) From Baseline to Week 12

Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12

Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12

Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12

Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12

Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12

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.

Minimum age: 18 Years. Maximum age: 68 Years. Gender(s): Both.

Criteria:

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

Freedom Trail Clinic, Boston, Massachusetts 02114, United States

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Starting date: June 2010
Last updated: March 26, 2014