Effects of Simvastatin on Biomarkers
Effects of Simvastatin on Biomarkers
Overall Status:
Recruiting
Brief Description:
This trial will test simvastatin, a drug approved to treat high cholesterol and reduce the risk of coronary artery disease, to see if it produces beneficial changes in Alzheimer's-related proteins in the cerebrospinal fluid of cognitively healthy, middle-aged adults.
Patient Qualifications:
| Min Age | Max Age | Gender | Healthy Volunteers |
|---|---|---|---|
45 Years | 64 Years | Both | Yes |
Inclusion Criteria:
- Cognitively normal with no evidence of memory or other cognitive impairments (MMSE > 26, Logical Memory delayed recall > 6, CDR score = 0)
- Normal or only mildly elevated cholesterol that does not require drug therapy
- Low-density lipoprotein (LDL) level above 70mg/dL
- Hamilton Depression Scale (HAM-D) score < 12
- Body Mass Index between 18 and 34 (exceptions possible)
- Good recent general health (no trauma or infection in the 4 weeks before lumbar puncture)
- On stable dose of allowable medications for at least 4 weeks preceding lumbar puncture
- Platelet count > 100,000
Exclusion Criteria:
- Pregnancy
- Any contraindications to lumbar puncture, such as spinal deformity, severe disease or infection in the lumbar puncture region, bleeding tendency, or anticoagulant or blood-thinning medications
- Taking or has taken a statin medication in the past 12 months
- Any clinically significant laboratory abnormalities
- Neurological disorders, including multiple sclerosis, epilepsy, stroke, Parkinson's disease, other degenerative central nervous system disorders, or neuropathy with radicular involvement
- Acute or chronic major psychiatric disorders, including schizophrenia, affective disorders, or severe anxiety disorders (dysthymia allowed, history of major depression allowed if currently in remission)
- Unstable or poorly controlled medical problems such as heart failure, diabetes (poorly controlled or insulin dependent), hypertension (blood pressure > 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 nonmelanoma skin cancer), or known HIV-positive status
- Use of illegal drugs or alcohol abuse (more than 2 drinks per day or 10 drinks per week) within the past year
- Concurrent participation in another investigational drug study
-
Prohibited medications:
- Drugs that could interact with statins (itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, amiodarone, cyclosporine, isoniazid, quinidine, or more than 1 quarter per day of grapefruit juice)
- Medications that act on the central nervous system (antipsychotics, Parkinson's disease medications, anticonvulsants, or central nervous system stimulants)
- Chronic use of benzodiazepines, sedating antihistamines, or other sedative-hypnotic agents (allowed as long as it is not within 72 hours of lumbar puncture or cognitive testing)
- Medications affecting coagulation and/or inflammation (coumadin, hydrocortisone, methotrexate or other potent immune-modulating medications, or 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)
- Family history of dementia: Both parents had/have dementia; on one side of the family, over two consecutive generations or three relatives had/have dementia; one parent with onset of dementia before age 60
- Major active autoimmune or immunological disorder
Detailed Description:
This study will assess whether simvastatin (brand name, Zocor), a drug used to treat high cholesterol and reduce the risk of coronary artery disease, beneficially affects the level of certain molecules, such as proteins, in the cerebrospinal fluid of cognitively normal, middle-aged adults. The molecules the investigators are measuring are thought to be important in the development of Alzheimer's disease. The investigators are testing whether simvastatin can change proteins to a level associated with reduced risk of Alzheimer's.
Participants will be randomly assigned to take simvastatin or a placebo for up to 1 year. Participants will be asked to come to the VA in Seattle a total of nine times, including twice for lumbar punctures (spinal taps). The investigators will also ask participants' spouses, children, or others who know them well about participants' health, memory, mood and behavior, and daily functioning.
Locations:
| Map Marker | City | State | Zip Code | Status | Primary Contact | |
|---|---|---|---|---|---|---|
Geolocation is 47.5405059, -122.3045438 | VA Puget Sound Health Care System | Seattle | Washington | 98108 | Recruiting |
Lead Sponsor:
| Agency |
|---|
University of Washington |
Collaborator Sponsor:
| Agency |
|---|
Seattle Institute for Biomedical and Clinical Research |
VA Puget Sound Health Care System |
Facility Investigators:
| Name | Role | Affiliation |
|---|---|---|
Gail Li, MD, PhD | Principal Investigator | University of Washington |
Study Contact:
| Name | Phone | |
|---|---|---|
Dan Morelli | 206-764-2581 |
Locations
ClinicalTrials.gov ID
NCT01142336 (follow link to view full record on ct.gov in new window)
Official Title:
Effects of Simvastatin on CSF AD Biomarkers in Cognitively Normal Subjects
Study Start Date:
June 2010
Study End Date:
June 2014
Enrollment:
120
