Clinical trial NCT00053599: Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer's Disease Study
Official title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial of Simvastatin to Slow the Progression of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: Cholesterol-lowering drug
Mild to Moderate Alzheimer disease
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
Collaborators: name: Alzheimer's Disease Cooperative Study (ADCS)
First posted: 2003-02-04
Enrollment: 400
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: * 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurology Group
state: Arizona
city: Tucson
country: United States
facility: Arizona Health Sciences Center, University of Arizona
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University/VA Aging Clinical Research Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University, Memory Disorder Program
state: District of Columbia
city: Washington
country: United States
facility: Howard University
state: District of Columbia
city: Boca Raton
country: United States
facility: Baumel Eisner Neuromedical Institute
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic (Jacksonville)
state: Florida
city: Miami Beach
country: United States
facility: Wein Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush Alzheimer's Disease Center, Rush University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Alzheimer's Center
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky, Sanders-Brown Center on Aging
state: Kentucky
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan at Ann Arbor
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: St. Louis
country: United States
facility: Washington University, St. Louis School of Medicine
state: Missouri
city: Brooklyn
country: United States
facility: SUNY Downstate
state: New York
city: New York
country: United States
facility: New York University School Of Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Stonybrook
country: United States
facility: SUNY Stony Brook
state: New York
city: Syracuse
country: United States
facility: Neurological Care of NY
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Memory and Aging Center, Case Western Reserve University/University Hospitals of Cleveland
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine, Alzheimer's Disease Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Brown University-Memorial Hospital of Rhode Island
state: Rhode Island
city: North Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas, Southwestern Medical School
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, Alzheimer's Disease Research Center
state: Texas
city: Bennington
country: United States
facility: Southwestern Vermont Medical Center
state: Vermont
city: Seattle
country: United States
facility: University of Washington at Seattle
state: Washington
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Mary Sano, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Leon J. Thal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hartmann T. Cholesterol, A beta and Alzheimer's disease. Trends Neurosci. 2001 Nov;24(11 Suppl):S45-8. doi: 10.1016/s0166-2236(00)01990-1.
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. doi: 10.1016/s0140-6736(00)03155-x.
citation: Simons M, Schwarzler F, Lutjohann 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. doi: 10.1002/ana.10292.