Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer's Disease Study

Alzheimer Disease Clinical Trial

Official title:

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial of Simvastatin to Slow the Progression of Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00053599
• Other study ID #: IA0038
• Secondary ID: ADC-015-LL
• Status: Completed
• Phase: Phase 3
• First received: February 3, 2003
• Last updated: July 24, 2009
• Start date: December 2002
• Est. completion date: October 2007

Study information

• Verified date: June 2009
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

CLASP is a research study to investigate the safety and effectiveness of simvastatin (a cholesterol lowering drug or statin) to slow the progression of Alzheimer's disease (AD). Statins are commonly used to treat high cholesterol levels, which increase the risk of heart disease and stroke.

Description:

In earlier studies in animals and humans, researchers found that lowering cholesterol levels with statins seems to have a positive impact on brain function and reduces the risk of AD. The CLASP trial will test the link between using a cholesterol lowering medication and slowing disease progress in people with mild to moderate Alzheimer's disease (AD).

CLASP is a research study to investigate the safety and effectiveness of simvastatin (a cholesterol lowering drug or statin) to slow the progression of AD. The clinical trial will include the treatment of patients with mild to moderate AD, and the objective is to evaluate the safety and efficacy of simvastatin to slow the progression of AD, as measured by the cognitive portion of the AD Assessment Scale. Measures of clinical global change (ADCS-CGIC), mental status, functional ability, behavioral disturbances, quality of life and economic indicators will be made also. The study design is randomized, double-blind, placebo-controlled, parallel group design with equal randomization to drug and placebo. Randomization will be stratified and blocked to ensure balanced assignment within site. Sample size will include 400 participants enrolled from approximately 40 sites with a goal of 10 to 15 volunteers enrolled at each site. Study medication will be as follows: 20 mg of simvastatin or matching placebo to be given for 6 weeks, followed by 40 mg of simvastatin or matching placebo for the remainder of the 18-month study period. Participants will be instructed to take the medication once a day in the evening. Safety parameters to be checked will include adverse events, symptom checklists, vital signs, physical and neurological examinations, and laboratory tests.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

• Mild to moderate patients with AD who are free of life-threatening disease and who do not require lipid-lowering treatment according to current guidelines.

• NINCDS/ADRDA criteria for probable AD.

• Mini-Mental-State-Exam (MMSE) score between 12 and 26.

• Stable medical condition for 3 months prior to the screening visit.

• Age greater than or equal to 50 years, and no upper age limit.

• Lives in a community dwelling, not in a nursing home.

• Stable doses of (non-excluded) medications with central nervous system activity for 4 weeks prior to the screening visit.

• Physical condition acceptable for the study as confirmed by medical history, physical exam, neurologic exam and clinical laboratory tests.

• Informant/study partner available and willing to accompany participant to all scheduled visits and complete informant-based assessments and to supervise administration of study medications.

• Fluent in English or Spanish.

• Modified Hachinski is less than or equal to 4.

Exclusion criteria:

• Coronary heart disease (CHD) including angina, or peripheral vascular disease including symptomatic carotid artery disease, or stroke or TIA, as these individuals are likely to require treatment with lipid-lowering drugs.

• Serious renal disease.

• Uncontrolled diabetes.

• Triglycerides are greater than 500 mg/dL.

• LDL-Cholesterol below 80 mg/dL

• Upper limit for the National Cholesterol Education Program (NCEP) guidelines for LDL-Cholesterol is 130-190 mg/dL, depending on age and other cardiovascular risk factors.

• Other indication for the need to treat with lipid-lowering drug.

• Active liver disease or persistent elevation in serum transaminase.

• Active neoplastic disease (skin tumors other than melanoma are not exclusionary; subjects with stable prostate cancer may be included at the discretion of the Project Director).

• Use of another investigational agent within 2 months of the screening visit.

• History of clinically significant stroke.

• Current evidence or history in the past 2 years of seizures, head injury with loss of consciousness and/or immediate confusion after the injury.

• Current DSM-IV criteria based diagnosis for major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse.

• Blindness, deafness, language difficulties or any other disability which may prevent the subject from participating or cooperating in the protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Simvastatin

Locations

Country	Name	City	State
United States	University of Michigan at Ann Arbor	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Southwestern Vermont Medical Center	Bennington	Vermont
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Baumel Eisner Neuromedical Institute	Boca Raton	Florida
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	SUNY Downstate	Brooklyn	New York
United States	Northwestern University	Chicago	Illinois
United States	Rush Alzheimer's Disease Center, Rush University	Chicago	Illinois
United States	University Memory and Aging Center, Case Western Reserve University/University Hospitals of Cleveland	Cleveland	Ohio
United States	University of Texas, Southwestern Medical School	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine, Alzheimer's Disease Research Center	Houston	Texas
United States	Indiana University Alzheimer's Center	Indianapolis	Indiana
United States	University of California, Irvine	Irvine	California
United States	Mayo Clinic (Jacksonville)	Jacksonville	Florida
United States	University of California, San Diego	La Jolla	California
United States	University of Kentucky, Sanders-Brown Center on Aging	Lexington	Kentucky
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Wein Center	Miami Beach	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	New York University School Of Medicine	New York	New York
United States	Medical University of South Carolina	North Charleston	South Carolina
United States	Stanford University/VA Aging Clinical Research Center	Palo Alto	California
United States	University of Pennsylvania School of Medicine, Alzheimer's Disease Center	Philadelphia	Pennsylvania
United States	Barrow Neurology Group	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Brown University-Memorial Hospital of Rhode Island	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California, Davis	Sacramento	California
United States	University of Washington at Seattle	Seattle	Washington
United States	St. Louis University	St. Louis	Missouri
United States	Washington University, St. Louis School of Medicine	St. Louis	Missouri
United States	SUNY Stony Brook	Stonybrook	New York
United States	Neurological Care of NY	Syracuse	New York
United States	Arizona Health Sciences Center, University of Arizona	Tucson	Arizona
United States	Georgetown University, Memory Disorder Program	Washington	District of Columbia
United States	Howard University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)	Alzheimer's Disease Cooperative Study (ADCS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Hartmann T. Cholesterol, A beta and Alzheimer's disease. Trends Neurosci. 2001 Nov;24(11 Suppl):S45-8. Review. — View Citation

Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000 Nov 11;356(9242):1627-31. Erratum in: Lancet 2001 Feb 17;357(9255):562. — View Citation

Simons M, Schwärzler F, Lütjohann D, von Bergmann K, Beyreuther K, Dichgans J, Wormstall H, Hartmann T, Schulz JB. Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol. 2002 Sep;52(3):346-50. — View Citation

External Links

•   Alzheimer's Disease Cooperative Study