Effects of Statin Medications on Mental Processes, Behavior, and Serotonin Levels

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ClinicalTrials.gov Identifier: NCT00330980

Recruitment Status : Completed

First Posted : May 29, 2006

Last Update Posted : March 20, 2014

Sponsor:

Collaborator:

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by:

University of California, San Diego

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Dyslipidemias	Drug: 40 mg Pravastatin (Pravachol) Drug: 20 mg Simvastatin Drug: Placebo	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1000 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Statins and Noncardiovascular Endpoints
Study Start Date :	April 2000
Actual Primary Completion Date :	March 2004
Actual Study Completion Date :	March 2004

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cholesterol Medicines Statins

Drug Information available for: Simvastatin Pravastatin

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Participants will receive 20 mg of simvastatin for 6 months.	Drug: 20 mg Simvastatin Participants will receive 20 mg of simvastatin for 6 months.
Experimental: 2 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.
Placebo Comparator: 3 Participants will receive placebo for 6 months.	Drug: Placebo Participants will receive placebo for 6 months.

Outcome Measures

Primary Outcome Measures :

Effects of statins on cognition, serotonin biochemistry, and aggression [ Time Frame: Measured at Months 6 and 8 ]

Secondary Outcome Measures :

Effect of statins on mood, and other cognitive, behavioral, and biochemical measures [ Time Frame: Measured at Months 6 and 8 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	20 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00330980

Locations

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

Sponsors and Collaborators

University of California, San Diego

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

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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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Golomb BA, Dimsdale JE, Koslik HJ, Evans MA, Lu X, Rossi S, Mills PJ, White HL, Criqui MH. Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial. PLoS One. 2015 Jul 1;10(7):e0124451. doi: 10.1371/journal.pone.0124451. eCollection 2015.

Golomb BA, Chan VT, Evans MA, Koperski S, White HL, Criqui MH. The older the better: are elderly study participants more non-representative? A cross-sectional analysis of clinical trial and observational study samples. BMJ Open. 2012 Dec 14;2(6). pii: e000833. doi: 10.1136/bmjopen-2012-000833. Print 2012.

Golomb BA, Koperski S, White HL. Association between more frequent chocolate consumption and lower body mass index. Arch Intern Med. 2012 Mar 26;172(6):519-21. doi: 10.1001/archinternmed.2011.2100.

Golomb BA, Evans MA, White HL, Dimsdale JE. Trans fat consumption and aggression. PLoS One. 2012;7(3):e32175. doi: 10.1371/journal.pone.0032175. Epub 2012 Mar 5.

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. doi: 10.1001/archinte.168.7.721.

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Responsible Party:	Beatrice A. Golomb, MD, PhD, University of California, San Diego
ClinicalTrials.gov Identifier:	NCT00330980
Other Study ID Numbers:	394 R01HL063055 ( U.S. NIH Grant/Contract )
First Posted:	May 29, 2006 Key Record Dates
Last Update Posted:	March 20, 2014
Last Verified:	July 2008

Keywords provided by University of California, San Diego:


Cognition Statins Serotonin Cholesterol

Additional relevant MeSH terms:

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Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Simvastatin Pravastatin Anticholesteremic Agents	Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors

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