Evaluating Simvastatin's Potential Role in Therapy

NCT ID: NCT00486044

Last Updated: 2019-03-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-02-28

Study Completion Date

2009-06-30

Brief Summary

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The purpose of this study is to see how simvastatin, a cholesterol-lowering drug, affects processes related to the development of Alzheimer's disease, including: 1) levels of a substance called beta-amyloid-42 found in the spinal fluid surrounding the brain, 2) blood flow in the brain, 3) inflammation in the brain, and 4) cognitive function.

Detailed Description

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Some studies suggest that statin medications, which are a group of cholesterol-lowering medicines, may help prevent Alzheimer's disease. However, this has not been proven in humans. The purpose of this study is to see how simvastatin affects a substance in the spinal fluid around the brain called beta-amyloid-42 which is thought to contribute to Alzheimer's disease. This study also evaluates whether simvastatin improves regional brain blood flow (on magnetic resonance imaging \[MRI\]), reduces inflammation, and improves cognitive function.

The ESPRIT study was a 9-month randomized, controlled clinical trial that randomized 100 middle-aged adults with a parental history of Alzheimer's disease. Participants were randomized to simvastatin 40 mg for one month then 80 mg daily or matching placebo tablets. Fifty of the ESPRIT subjects participated in the MRI sub-study.

Participants had the following data collected: fasting blood tests (baseline and months 3 and 9), medical history and medication questionnaires (each visit), study medication side effect review (all visits), lumbar puncture procedure (baseline and month 9), memory testing (baseline and months 3 and 9), and MRI (baseline and month 9 in 50 sub-study participants).

Conditions

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Alzheimer Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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simvastatin

simvastatin 40 mg nightly for 1 month then 80 mg nightly for 8 months

Group Type EXPERIMENTAL

Simvastatin

Intervention Type DRUG

40 mg tablet each night for one month, then 80 mg for 8 months

Placebo

Matching placebo tablet nightly for 9 months

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching tablet each night for 9 months

Interventions

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Simvastatin

40 mg tablet each night for one month, then 80 mg for 8 months

Intervention Type DRUG

Placebo

Matching tablet each night for 9 months

Intervention Type DRUG

Other Intervention Names

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Zocor

Eligibility Criteria

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Inclusion Criteria

* Age 35 to 69
* Parent with Alzheimer's disease

Exclusion Criteria

* Current use of cholesterol-lowering medication
* Active liver disease
* History of adverse reaction to statins
* Contraindication to lumbar puncture
* Elevated lab values (creatine kinase and creatinine)
* Use of medications known to interact with statins
* History of dementia
* Currently pregnant or planning to become pregnant
* Use of large quantities of grapefruit juice (more than 1 quart per day)
* Current involvement in another investigational drug study
* Contraindications to MRI (for MRI sub-study)
* Ethical contraindication to placebo (persons with high vascular risk)
Minimum Eligible Age

35 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Paul Beeson Faculty Scholars Program

OTHER

Sponsor Role collaborator

The John A. Hartford Foundation

OTHER

Sponsor Role collaborator

The Atlantic Philanthropies

OTHER

Sponsor Role collaborator

Starr Foundation

OTHER

Sponsor Role collaborator

American Federation for Aging Research

OTHER

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cynthia M. Carlsson, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

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University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5856-61. doi: 10.1073/pnas.081620098. Epub 2001 Apr 10.

Reference Type BACKGROUND
PMID: 11296263 (View on PubMed)

Wolozin B. A fluid connection: cholesterol and Abeta. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5371-3. doi: 10.1073/pnas.101123198. No abstract available.

Reference Type BACKGROUND
PMID: 11344276 (View on PubMed)

Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology. 2005 Mar;234(3):851-9. doi: 10.1148/radiol.2343040197.

Reference Type BACKGROUND
PMID: 15734937 (View on PubMed)

Related Links

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http://adrc.wisc.edu/

Wisconsin Alzheimer's Disease Research Center

Other Identifiers

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1K23AG026752-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IA0116

Identifier Type: -

Identifier Source: org_study_id

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