Clinical trial NCT00486044: Evaluating Simvastatin's Potential Role in Therapy
Official title: Effect of Statins on Pathobiology of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Keywords: amyloid protein
apolipoprotein
cerebrospinal fluid
cerebrovascular circulation
inflammation
magnetic resonance imaging
prevention & control
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Paul Beeson Faculty Scholars Program
name: The John A. Hartford Foundation
name: The Atlantic Philanthropies
name: Starr Foundation
name: American Federation for Aging Research
name: Merck Sharp & Dohme LLC
First posted: 2007-06-13
Enrollment: 103
Sex: ALL
Minimum age (years): 35
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42
timeFrame: baseline and 9 months
Secondary outcomes:
measure: Changes in Regional Cerebral Blood Flow on MRI
timeFrame: baseline and 9 months
measure: Change in Inflammatory Markers
timeFrame: baseline and 9 months
measure: Changes in Cognitive Performance
timeFrame: Baseline and 9 months
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Cynthia M. Carlsson, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.