Clinical trial NCT01142336: Effects of Simvastatin on Biomarkers
Official title: Effects of Simvastatin on CSF AD Biomarkers in Cognitively Normal Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Prevention
Spinal Fluid
Biomarkers
Simvastatin
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Seattle Institute for Biomedical and Clinical Research
name: VA Puget Sound Health Care System
First posted: 2010-06-11
Enrollment: 49
Sex: ALL
Minimum age (years): 45
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: The purpose of this study is to see if a drug called simvastatin (brand name Zocor) beneficially affects the level of certain molecules (such as proteins) in the spinal fluid of people. The molecules the investigators are measuring are thought to be important in the development of Alzheimer's disease (AD), and the investigators are testing whether simvastatin can change proteins to a level that is associated with a reduced risk for AD.

Simvastatin has been approved by the United States Food and Drug Administration (FDA) for the treatment of high cholesterol and to reduce the risk of coronary artery disease. It is an investigational drug in this study.

Participants will be randomly assigned to Placebo or Simvastatin. The investigators and the participant will be blinded. Randomization will be stratified by age and gender.

This study is being funded by the National Institute on Aging. The investigators will take part in this study at the VA Puget Sound Health Care System.

This study will last up to 1 year. Participants will be asked to come to the VA in Seattle a total of 9 times, 2 of those times will be for lumbar punctures (also known as a spinal tap).

The investigators would also like to ask a person who knows the participant well (such as a spouse, child, sibling, or good friend) some questions about the participant's health, memory, mood and behavior, and abilities to do daily tasks at the beginning and the end of the study.

Participants must be cognitively normal, healthy, willing to have a lumbar puncture, and not need or take any medications to control cholesterol.

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?

Primary outcomes:
measure: Change From Baseline in Aβ42 in Cerebrospinal Fluid (CSF) at 1 Year
timeFrame: 1-year change of CSF Aβ42 from baseline
measure: Change From Baseline in CSF Total Tau at 1 Year
timeFrame: 1-yr change
measure: Change From Baseline in CSF ptau181 at 1 Year
timeFrame: 1-year change from baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
Study officials:
affiliation: University of Washington
name: Gail Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: