Effects of Simvastatin on Biomarkers

• Status: Completed
• Trial end date: 2015-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Washington
• Collaborators: Seattle Institute for Biomedical and Clinical Research; VA Puget Sound Health Care System
• Treatments: Simvastatin

Criteria

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?