Evaluating Simvastatin's Potential Role in Therapy

NCT00486044 | Completed Phase 2 Results DMC

• 2 other identifiers: IA01161K23AG026752-01
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Keywords

amyloid protein; apolipoprotein; cerebrospinal fluid; cerebrovascular circulation; inflammation; magnetic resonance imaging; prevention & control

Outcome Measures

Primary Outcomes (1)

• Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42

  baseline and 9 months

Secondary Outcomes (3)

• Changes in Regional Cerebral Blood Flow on MRI

  baseline and 9 months

• Change in Inflammatory Markers

  baseline and 9 months

• Changes in Cognitive Performance

  Baseline and 9 months

Study Arms (2)

simvastatin

EXPERIMENTAL

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

Drug: Simvastatin

Placebo

PLACEBO COMPARATOR

Matching placebo tablet nightly for 9 months

Drug: Placebo

Interventions

Simvastatin DRUG

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

Also known as: Zocor

simvastatin

Placebo DRUG

Matching tablet each night for 9 months

Placebo

Eligibility Criteria

• Age: 35 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute on Aging (NIA): collaborator
• Paul Beeson Faculty Scholars Program: collaborator
• The John A. Hartford Foundation: collaborator
• The Atlantic Philanthropies: collaborator
• Starr Foundation: collaborator
• American Federation for Aging Research: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Related Publications (3)

• 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.

  PMID: 11296263 BACKGROUND

• 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.

  PMID: 11344276 BACKGROUND

• 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.

  PMID: 15734937 BACKGROUND

Related Links

• Wisconsin Alzheimer's Disease Research Center

MeSH Terms

Conditions

Alzheimer Disease; Amyloidosis; Inflammation

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Cynthia M. Carlsson, MD, MS
• Organization: University of Wisconsin School of Medicine and Public Health

cmc@medicine.wisc.edu

608-280-7000

Study Officials

• Cynthia M. Carlsson, MD, MS

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2007
• First Posted: June 13, 2007
• Study Start: February 1, 2005
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: March 5, 2019
• Results First Posted: November 5, 2015

Record last verified: 2019-02

Locations

US (1)