Evaluating Simvastatin's Potential Role in Therapy - Full Text View

Sponsor:	National Institute on Aging (NIA)
Collaborators:	Paul Beeson Faculty Scholars Program The John A. Hartford Foundation The Atlantic Philanthropies Starr Foundation American Federation for Aging Research Merck
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00486044

Purpose

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 fluid surrounding the brain, 2) blood flow in the brain, 3) inflammation in the brain, and 4) the brain's handling of cholesterol.

Condition	Intervention	Phase
Alzheimer Disease	Drug: Simvastatin Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Effect of Statins on Pathobiology of Alzheimer's Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Cholesterol

Drug Information available for: Simvastatin

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:

Changes in cerebrospinal fluid beta-amyloid levels [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in biomarkers of CNS cholesterol metabolism, inflammatory markers, and cerebral perfusion [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Changes in cognitive function [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	February 2005
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Simvastatin 40 mg tablet each night for one month, then 80 mg for 8 months
2: Placebo Comparator	Drug: Placebo Matching tablet each night for 9 months

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 substances in the body called beta-amyloid 40 and beta-amyloid 42, as well as blood flow to the brain. These substances are found in both the brain and the fluid around the brain and spinal cord. High amounts of these substances may be associated with a greater risk of getting Alzheimer's disease.

The ESPRIT study will include 100 middle-aged adults (35-69 yrs) who have a parent with documented Alzheimer's disease. This study will see how the use of a particular statin medication, simvastatin, affects spinal fluid levels of beta-amyloid, inflammation, and cholesterol. In addition, these changes will be compared to changes in memory and thinking skills monitored throughout the study. Fifty of the ESPRIT subjects will also participate in the MRI substudy, which is examining the effects of the study medication on blood flow to structures in the brain that are associated with Alzheimer's disease.

Participants will take part in 5 visits (and an additional 2 visits, if participating in the MRI substudy) over the course of 9 months. Participants will undergo fasting blood tests (baseline, month 3, and month 9 visits), complete a medical history questionnaire (baseline), complete medication side effect review through questionnaire and/or blood sample (all visits), undergo lumbar puncture procedure (baseline and month 9 visits), complete memory testing (baseline, month 3 and month 9 visits), and MRI procedure (baseline and month 9 visits), if participating in MRI substudy. Participants will be randomly assigned to receive either simvastatin or a placebo each night for 9 months.

Eligibility

Ages Eligible for Study:	35 Years to 69 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age 35 to 69
Parent with Alzheimer's disease

Exclusion Criteria:

Current use of cholesterol lowering medication
History of liver disease
History of adverse reaction to statin medications
History of previous lumbar spine surgery
Elevated lab values (creatine kinase and creatinine)
Use of prohibited medications: Simvastatin, Pravastatin, Cholestyramine, Lovastatin, Colestipol, Gemfibrozil, Niacin, Atorvastatin, Fluvastatin, Fenofibrate, Rosuvastatin, Clarithromycin, Cyclosporine, Digoxin, Erythromycin, Itraconazole, Ketaconazole, Fluconazole, Nefazodone, Warfarin, Saquinavir, Ritonavir, Indinavir, Nelfinavir, Amprenavir, Amiodarone, Verapamil
History of dementia
Currently pregnant
Use of large quantities of grapefruit juice (more than 1 quart per day)
Current involvement in another investigational drug study
Contraindications to MRI

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486044

Locations

United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705

Sponsors and Collaborators

National Institute on Aging (NIA)

Paul Beeson Faculty Scholars Program

The John A. Hartford Foundation

The Atlantic Philanthropies

Starr Foundation

American Federation for Aging Research

Merck

Investigators

Principal Investigator:

Cynthia M. Carlsson, MD, MS

University of Wisconsin School of Medicine and Public Health

More Information

Additional Information:

Wisconsin Comprehensive Memory Program This link exits the ClinicalTrials.gov site

Publications:

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. Epub 2001 Apr 10.

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

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.

Responsible Party:	University of Wisconsin School of Medicine and Public Health ( Cynthia M. Carlsson, MD, MS, Assistant Professor of Medicine )
Study ID Numbers:	IA0116, 1K23AG026752-01
Study First Received:	June 12, 2007
Last Updated:	June 30, 2009
ClinicalTrials.gov Identifier:	NCT00486044 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

amyloid protein
apolipoprotein
central nervous system
disease /disorder proneness /risk
inflammation

Additional relevant MeSH terms:

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Simvastatin
Antilipemic Agents
Alzheimer Disease
Nervous System Diseases
Central Nervous System Diseases
Enzyme Inhibitors
Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Brain Diseases
Neurodegenerative Diseases
Pharmacologic Actions
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Therapeutic Uses
Dementia
Tauopathies

ClinicalTrials.gov processed this record on November 09, 2009