Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

This study has been completed.
Sponsor:
Collaborators:
Paul Beeson Faculty Scholars Program
The John A. Hartford Foundation
The Atlantic Philanthropies
Starr Foundation
American Federation for Aging Research
Merck Sharp & Dohme Corp.
Information provided by:
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00486044
First received: June 12, 2007
Last updated: September 27, 2010
Last verified: September 2010
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Statins on Pathobiology of Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

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
Experimental: 1 Drug: Simvastatin
40 mg tablet each night for one month, then 80 mg for 8 months
Other Name: Zocor
Placebo Comparator: 2 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
University of Wisconsin, Madison
Paul Beeson Faculty Scholars Program
The John A. Hartford Foundation
The Atlantic Philanthropies
Starr Foundation
American Federation for Aging Research
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Cynthia M. Carlsson, MD, MS University of Wisconsin, Madison
  More Information

Additional Information:
Publications:
Responsible Party: Cynthia M. Carlsson, MD, MS, Assistant Professor of Medicine, University of Wisconsin School of Medicine and Public Health
ClinicalTrials.gov Identifier: NCT00486044     History of Changes
Other Study ID Numbers: IA0116, 1K23AG026752-01
Study First Received: June 12, 2007
Last Updated: September 27, 2010
Health Authority: United States: Federal Government

Keywords provided by University of Wisconsin, Madison:
amyloid protein
apolipoprotein
central nervous system
disease /disorder proneness /risk
inflammation

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014