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

Dyslipidemias Clinical Trial

Official title:

Statins and Noncardiovascular Endpoints

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00330980
• Other study ID #: 394
• Secondary ID: R01HL063055
• Status: Completed
• Phase: Phase 4
• First received: May 26, 2006
• Last updated: March 19, 2014
• Start date: April 2000
• Est. completion date: March 2004

Study information

• Verified date: July 2008
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: March 2004
• Est. primary completion date: March 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Dyslipidemias

Intervention

Drug:
• 40 mg Pravastatin (Pravachol)
Participants will receive 40 mg of pravastatin for 6 months.
• 20 mg Simvastatin
Participants will receive 20 mg of simvastatin for 6 months.
• Placebo
Participants will receive placebo for 6 months.

Locations

Country	Name	City	State
United States	University of California, San Diego	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effects of statins on cognition, serotonin biochemistry, and aggression		Measured at Months 6 and 8	No
Secondary	Effect of statins on mood, and other cognitive, behavioral, and biochemical measures		Measured at Months 6 and 8	No