Effects of Statin Medications on Mental Processes, Behavior, and Serotonin Levels - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00330980

Purpose

Statins are cholesterol-lowering medications that are often prescribed for individuals with high cholesterol and who are at risk for heart disease.

Preliminary research has shown that statins may have other effects on the body that are unrelated to the heart. The purpose of this study is to evaluate the impact of statins on mood, mental processes, aggression, and serotonin levels.

Condition	Intervention	Phase
Dyslipidemias	Drug: 40 mg Pravastatin (Pravachol) Drug: 20 mg Simvastatin Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Pharmacodynamics Study
Official Title:	Statins and Noncardiovascular Endpoints

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Statins

Drug Information available for: Serotonin Simvastatin Pravastatin Pravastatin sodium

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Effects of statins on cognition, serotonin biochemistry, and aggression [ Time Frame: Measured at Months 6 and 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Effect of statins on mood, and other cognitive, behavioral, and biochemical measures [ Time Frame: Measured at Months 6 and 8 ] [ Designated as safety issue: No ]

Estimated Enrollment:	1000
Study Start Date:	April 2000
Study Completion Date:	March 2004
Primary Completion Date:	March 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive 20 mg of simvastatin for 6 months.	Drug: 20 mg Simvastatin Participants will receive 20 mg of simvastatin for 6 months.
2: Experimental Participants will receive 40 mg of pravastatin for 6 months.	Drug: 40 mg Pravastatin (Pravachol) Participants will receive 40 mg of pravastatin for 6 months.
3: Placebo Comparator Participants will receive placebo for 6 months.	Drug: Placebo Participants will receive placebo for 6 months.

Detailed Description:

Individuals at risk for coronary artery disease are often prescribed statins, which are medications that reduce the amount of cholesterol in the blood.

By lowering cholesterol levels, these individuals have a lower incidence of heart disease, heart attacks, and stroke. Simvastatin and pravastatin are two common statins that are often prescribed for individuals with high cholesterol. While statins are effective at lowering cholesterol levels, their effect on mood, behavior, and aggression has not been widely studied. Preliminary research has shown that lowering cholesterol levels may lead to an increase in aggressive behaviors and a change in cognitive function. Serotonin, a type of neurotransmitter, is believed to play an important role in the regulation of mood, as well as behavior and cognition. The direct effect of statins on serotonin levels remains unknown. The purpose of this study is to evaluate the effect of simvastatin and pravastatin on mood, cognition, aggression, and serotonin levels.

This study will enroll individuals who do not currently take cholesterol-lowering medications. Participants will be randomly assigned to receive 20 mg of simvastatin, 40 mg of pravastatin, or placebo for 6 months. Study visits will occur at baseline and Months 1, 3, 6, and 8. Height, weight, and waist circumference will be measured at all study visits. Blood and urine will be collected for laboratory testing, and standardized psychological questionnaires will assess cognition, aggression, mental flexibility, memory, depression, sleep quality, and quality of life at Months 1, 6, and 8. At Month 3, medication side effects will be monitored and a liver function test will be performed. Participants' partners will take part in a telephone interview at this time. At baseline and Month 6, some participants will undergo cardiac reactivity testing. During this procedure, participants will be videotaped and monitored for vital sign changes (blood pressure and heart rate) while they talk about potentially stressful situations.

Eligibility

Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

LDL cholesterol level between 115-190 mg/dL
Able to fast prior to blood draw
Able to comfortably read and write in English
Able and willing to refrain from donating whole blood during study participation
Willing to abstain from consuming large amounts of grapefruit juice

Exclusion Criteria:

Current use of lipid-lowering medications
Symptomatic atherosclerotic disease, such as coronary artery disease, kidney failure or insufficiency, peripheral arterial disease, or cerebrovascular disease
Cancer
HIV infected
Medical or psychiatric condition that prevents full study participation or follow-up (e.g., active psychosis)
Active liver disease or unexplained persistent elevated transaminase levels
Major surgery or hospitalization in the 3 months prior to study entry
Current use of cyclosporin, erythromycin, clarithromycin, nefazodone, or any "azole" antifungals, including fluconazole, itraconazole, ketoconazole, mibefradil, or protease inhibitors
Female of childbearing potential
Current participation in another clinical trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00330980

Locations

United States, California
University of California, San Diego
La Jolla, California, United States, 92093-0995

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Beatrice A. Golomb, MD, PhD

University of California, San Diego

More Information

Publications:

Golomb BA, Criqui MH, White HL, Dimsdale JE. The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes. Control Clin Trials. 2004 Apr;25(2):178-202.

Golomb BA, Criqui MH, White H, Dimsdale JE. Conceptual foundations of the UCSD Statin Study: a randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry. Arch Intern Med. 2004 Jan 26;164(2):153-62. Review.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Golomb BA, Dimsdale JE, White HL, Ritchie JB, Criqui MH. Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial. Arch Intern Med. 2008 Apr 14;168(7):721-7.

Responsible Party:	University of California, San Diego ( Beatrice A. Golomb, MD, PhD )
Study ID Numbers:	394, R01 HL063055
Study First Received:	May 26, 2006
Last Updated:	July 29, 2008
ClinicalTrials.gov Identifier:	NCT00330980 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Cognition
Statins
Serotonin
Cholesterol

Study placed in the following topic categories:

Antimetabolites
Pravastatin
Metabolic Diseases
Simvastatin
Antilipemic Agents
Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Metabolic Disorder
Serotonin
Dyslipidemias
Lipid Metabolism Disorders

Additional relevant MeSH terms:

Antimetabolites
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Simvastatin
Antilipemic Agents
Enzyme Inhibitors
Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Pravastatin
Therapeutic Uses
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on July 02, 2009