Effects of Pravastatin on Cholesterol, Inflammation and Cognition in Schizophrenia

• ClinicalTrials.gov Identifier: NCT01082588
• Recruitment Status: Completed
• First Posted: March 8, 2010
• Results First Posted: April 28, 2014
• Last Update Posted: April 28, 2014
• Sponsor: Massachusetts General Hospital
• Collaborators: Stanley Medical Research Institute; North Suffolk Mental Health Association
• Information provided by (Responsible Party): David C. Henderson, Massachusetts General Hospital

Study Description

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

Condition or disease	Intervention/treatment	Phase
Schizophrenia; Schizoaffective Disorders; Schizophreniform Disorders	Drug: Pravastatin; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 4 Study of the Effects of Pravastatin on Cholesterol Levels, Inflammation and Cognition in Schizophrenia
• Study Start Date: June 2010
• Actual Primary Completion Date: September 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: pravastatin; pravastatin 40mg, once a day, shortly after baseline for 12 consecutive weeks	Drug: Pravastatin; pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks; Other Names: pravastatin sodium; Pravachol
Placebo Comparator: Placebo; placebo, once a day, shortly after baseline for 12 consecutive weeks	Drug: Placebo; pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks

Outcome Measures

Primary Outcome Measures :

1. Change in LDL-cholesterol Between Baseline and Week 12 [ Time Frame: Baseline, week 12 ]
2. Change in C-Reactive Protein (CRP) From Baseline to Week 12 [ Time Frame: Baseline, week 12 ]
3. Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12 [ Time Frame: 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.

4. Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12 [ Time Frame: 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.
5. Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12 [ Time Frame: 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.
6. Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12 [ Time Frame: 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.
7. Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 68 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Massachusetts

Freedom Trail Clinic

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Stanley Medical Research Institute

North Suffolk Mental Health Association

Investigators

• Principal Investigator: David C Henderson, M.D.; Massachusetts General Hospital

More Information

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• Responsible Party: David C. Henderson, Associate Professor of Psychiatry, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01082588
• Obsolete Identifiers: NCT01363219
• Other Study ID Numbers: 2009-P-002524; 09T-1296 ( Other Grant/Funding Number: Stanley Medical Research Institute )
• First Posted: March 8, 2010
• Results First Posted: April 28, 2014
• Last Update Posted: April 28, 2014
• Last Verified: March 2014

Keywords provided by David C. Henderson, Massachusetts General Hospital:

schizophrenia; pravastatin; inflammation; cognition; antipsychotics; cholesterol

Additional relevant MeSH terms:

Disease; Inflammation; Schizophrenia; Psychotic Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pravastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors