Alzheimer's Disease | Effects of Simvastatin on Biomarkers
Alzheimer's Disease research study
What is the primary objective of this study?
A year-long randomized, double-blind, placebo-controlled trial of simvastatin to see if it produces beneficial changes in cerebral spinal fluid proteins associated with Alzheimer's disease.
Who is eligible to participate?
Inclusion Criteria (participants must meet the following criteria) - If female of childbearing potential, must have negative pregnancy test at baseline, and all subsequent visits. - Age 45 to 64 years inclusive. - Considered cognitively normal with no evidence of memory or other cognitive impairments (MMSE >26, Logical Memory delayed recall > 6, CDR score of 0). - Normal or only mildly elevated cholesterol which does not require drug therapy based on National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP-III) guidelines. - An LDL level above 70mg/dL. - Hamilton Depression Scale (HAM-D) score < 12. - BMI between 18 - 34 (or exception made by MD). - In good recent general health (i.e., no trauma or infection in the 4 weeks before LP). - On stable dose of non-exclusionary medications for the 4 weeks preceding the LP. - Platelet count >100,000. Exclusion Criteria (participants must NOT satisfy any of the following conditions) - Any contraindications to LP, such as spinal deformity, severe disease or infection in the LP region, bleeding tendency, anticoagulant or blood-thinning medications. - Taken a statin medication in the past 12 months. - Any clinically significant laboratory abnormalities. - Any neurological disorders: multiple sclerosis, epilepsy, stroke, Parkinson's, other degenerative CNS disorders, or neuropathy with radicular involvement. - Acute or chronic major psychiatric disorders: schizophrenia, affective disorders, or severe anxiety disorders. (Dysthymia allowed, history of MDD allowed if currently in remission) - Unstable or poorly controlled medical problems such as: heart failure, diabetes (poorly controlled or insulin dependent), hypertension (BP >160/100), pulmonary disease with hypoxia or hypercapnia, significant liver disease or known hepatitis C seropositivity, renal failure, treatment for cancer in the past 2 years (other than non-melanoma skin cancer) or known HIV positive status. - Use of illegal drugs or alcohol abuse (>2 drinks/day or 10/week) within the past year. - Concurrent participation in another investigational drug study. - Use of any exclusionary medications in the 4 weeks prior to screening: - Drugs which could interact with statins: itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, amiodarone, cyclosporine, isoniazid, quinidine, or large quantities of grapefruit juice (>1 quart daily) - Central nervous system acting medications: antipsychotics, anti-Parkinson's disease medications, anti convulsants, or CNS stimulants - Chronic use of benzodiazepines, sedating antihistamines, or other sedative-hypnotic agents (prn use is allowed as long as it is not within 72 hours of LP or cognitive testing) - Medications affecting coagulation and/or inflammation: coumadin, potent anti-inflammatory medications (hydrocortisone, methotrexate or other potent immune-modulating medications), and anti-HIV medications (Aspirin up to 325 mg/day is allowed.) - Lipid-lowering drugs: fibrates or niacin >500mg/day (stable dose of omega-3 is allowed) - Does the subject's family history meet any of the following criteria? - Both parents had/have dementia - On one side of the family, over two consecutive generations three relatives had/have dementia? - One parent had an onset of dementia before age 60? - Does the subject have a major active autoimmune or immunological disorder?
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:SimvastatinSimvastatin 40mg qHS for 1 year
Drug:PlaceboPlacebo 1 tablet qHS for 1 year
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
SimvastatinSimvastatin 40mg qHS for 1 year
PlaceboPlacebo 1 tablet qHS for 1 year
Start Date: June 2010
Completed Date: October 2015
Phase: Phase 4
Primary Outcome: Change From Baseline in Aβ42 in Cerebrospinal Fluid (CSF) at 1 Year
Study sponsors, principal investigator, and references
Principal Investigator: Gail Li, MD, PhD
Lead Sponsor: University of Washington
Collaborator: Seattle Institute for Biomedical and Clinical Research