Effects of Simvastatin on Biomarkers
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Simvastatin; Placebo
Intervention description: Simvastatin 40mg qHS for 1 year; Placebo 1 tablet qHS for 1 year
Intervention MeSH terms: Simvastatin
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 49.0
Sex: All
Minimum age: 45 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Alzheimer's Disease; Prevention; Spinal Fluid; Biomarkers; Simvastatin

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.
    

Eligibility 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?