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

Sponsor

National Institute on Aging (NIA) (NIH)

Overall Status

Completed

CT.gov ID

NCT00053599

Collaborator

Alzheimer's Disease Cooperative Study (ADCS) (Other)

400

Enrollment

Locations

Duration (Months)

9.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Simvastatin	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2002

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Birmingham	Birmingham	Alabama	United States	35294-0017
2	Barrow Neurology Group	Phoenix	Arizona	United States	85013
3	Arizona Health Sciences Center, University of Arizona	Tucson	Arizona	United States	85724-5023
4	University of California, Irvine	Irvine	California	United States	92697-7016
5	University of California, San Diego	La Jolla	California	United States	92093-0948
6	University of Southern California	Los Angeles	California	United States	90093
7	University of California, Los Angeles	Los Angeles	California	United States	90095
8	Stanford University/VA Aging Clinical Research Center	Palo Alto	California	United States	94304
9	University of California, Davis	Sacramento	California	United States	95817
10	Yale University School of Medicine	New Haven	Connecticut	United States	06511
11	Georgetown University, Memory Disorder Program	Washington	District of Columbia	United States	20057
12	Howard University	Washington	District of Columbia	United States	20060
13	Baumel Eisner Neuromedical Institute	Boca Raton	Florida	United States	33486
14	Mayo Clinic (Jacksonville)	Jacksonville	Florida	United States	32224
15	Wein Center	Miami Beach	Florida	United States	33140
16	Emory University	Atlanta	Georgia	United States	30329
17	Northwestern University	Chicago	Illinois	United States	60611
18	Rush Alzheimer's Disease Center, Rush University	Chicago	Illinois	United States	60612
19	Indiana University Alzheimer's Center	Indianapolis	Indiana	United States	46202
20	University of Kentucky, Sanders-Brown Center on Aging	Lexington	Kentucky	United States	40536-0230
21	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
22	Boston University School of Medicine	Boston	Massachusetts	United States	02118
23	University of Michigan at Ann Arbor	Ann Arbor	Michigan	United States	48109-0504
24	Mayo Clinic	Rochester	Minnesota	United States	55901
25	St. Louis University	St. Louis	Missouri	United States	63104
26	Washington University, St. Louis School of Medicine	St. Louis	Missouri	United States	63108
27	SUNY Downstate	Brooklyn	New York	United States	11203
28	New York University School Of Medicine	New York	New York	United States	10016
29	Mount Sinai School of Medicine	New York	New York	United States	10029
30	Columbia University	New York	New York	United States	10032
31	University of Rochester Medical Center	Rochester	New York	United States	14642
32	SUNY Stony Brook	Stonybrook	New York	United States	11794-8121
33	Neurological Care of NY	Syracuse	New York	United States	13210
34	Duke University Medical Center	Durham	North Carolina	United States	27705
35	University Memory and Aging Center, Case Western Reserve University/University Hospitals of Cleveland	Cleveland	Ohio	United States	44120
36	Oregon Health and Sciences University	Portland	Oregon	United States	97201
37	University of Pennsylvania School of Medicine, Alzheimer's Disease Center	Philadelphia	Pennsylvania	United States	19104
38	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
39	Brown University-Memorial Hospital of Rhode Island	Providence	Rhode Island	United States	02903
40	Medical University of South Carolina	North Charleston	South Carolina	United States	29406
41	University of Texas, Southwestern Medical School	Dallas	Texas	United States	75390
42	Baylor College of Medicine, Alzheimer's Disease Research Center	Houston	Texas	United States	77030
43	Southwestern Vermont Medical Center	Bennington	Vermont	United States	05201
44	University of Washington at Seattle	Seattle	Washington	United States	98108