Effects of Simvastatin on Biomarkers (SimBio)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by University of Washington
Sponsor:
Collaborators:
Seattle Institute for Biomedical and Clinical Research
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Gail Li, University of Washington
ClinicalTrials.gov Identifier:
NCT01142336
First received: June 9, 2010
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
Alzheimer's Disease
Drug: Simvastatin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effects of Simvastatin on CSF AD Biomarkers in Cognitively Normal Subjects

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Cerebral Spinal Fluid Biomarker measurements [ Time Frame: Baseline, Year 1 ] [ Designated as safety issue: No ]
    Biomarkers of Alzheimer's Disease measured in cerebral spinal fluid: Aβ42, t-tau, p-tau181 and BDNF


Secondary Outcome Measures:
  • Measures of inflammation or oxidative stress in cerebral spinal fluid. [ Time Frame: Baseline, Year 1 ] [ Designated as safety issue: No ]
    Measures of inflammation or oxidative stress in cerebral spinal fluid: IL-6, IL-8, S100β, F2-isoprostanes, F4-neuroprostanes.


Estimated Enrollment: 120
Study Start Date: June 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Simvastatin
Simvastatin 40mg qHS for 1 year
Drug: Simvastatin
Simvastatin 40mg qHS for 1 year
Other Name: Zocor
Placebo Comparator: Placebo
Placebo 1 tablet qHS for 1 year
Drug: Placebo
Placebo 1 tablet qHS for 1 year
Other Name: Sugar Pill

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 expect about 120 people will take part in this study at the VA Puget Sound Health Care System over the course of a 2 year enrollment period.

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

Ages Eligible for Study:   45 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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?
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01142336

Contacts
Contact: Dan Morelli 206-764-2581 Daniel.Morelli@va.gov

Locations
United States, Washington
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98108
Contact: Dan Morelli    206-764-2581    Daniel.Morelli@va.gov   
Principal Investigator: Gail Li, MD, PhD         
Sponsors and Collaborators
University of Washington
Seattle Institute for Biomedical and Clinical Research
VA Puget Sound Health Care System
Investigators
Principal Investigator: Gail Li, MD, PhD University of Washington
  More Information

No publications provided

Responsible Party: Gail Li, Associate Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01142336     History of Changes
Other Study ID Numbers: 37373-B, 00183
Study First Received: June 9, 2010
Last Updated: September 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
Alzheimer's Disease
Prevention
Spinal Fluid
Biomarkers
Simvastatin

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014