Do HMG CoA Reductase Inhibitors Affect Abeta Levels?

NCT00303277 | Completed Phase 4 DMC

• 1 other identifier: 21974
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Recent evidence suggests that there is a significant overlap between AD and cerebrovascular disease. In fact, AD and cerebrovascular disease may share some of the same risk factors, including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up to 70%; however, effects differed by specific statin use. This study will compare two statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD and inflammatory markers. The primary aim of the proposed study is to determine whether there is a reduction in Abeta with statins and whether the ability of the statin to cross the blood-brain barrier will affect its ability to decrease Abeta. If it can be demonstrated that statins alter AD-associated biomarkers, this would have broad implications for the treatment and prevention of AD.

Conditions

Alzheimer's Disease; Aging

Keywords

Alzheimer's disease; beta-amyloid; statins

Outcome Measures

Primary Outcomes (1)

• CSF abeta levels

  baseline and 12 weeks

Secondary Outcomes (1)

• CSF biomarkers

  baseline and 12 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

simvastatin

Drug: simvastatin

2

ACTIVE COMPARATOR

pravastatin

Drug: pravastatin

Interventions

simvastatin DRUG

simvastatin 40 mg tablets once per day for 12 weeks

Also known as: Zocor

1

pravastatin DRUG

pravastatin 80 mg tablets once per day for 12 weeks

Also known as: Lipitor

2

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Total cholesterol \> 200, and/or LDL \> 130
• No cognitive impairment
• Statin-naive for at least one year
• Women must not be pregnant, nursing, or planning to become pregnant

You may not qualify if:

• Back ailments which would hinder LP procedure
• Neurological disease, including stroke, Parkinson's disease, Multiple Sclerosis, uncontrolled epilepsy, history of severe head trauma
• Hepatic disease
• Renal insufficiency
• Unstable medical disease
• Severe pulmonary disease
• Severe cardiac disease
• Uncontrolled hypertension (greater than 160/90)
• Uncontrolled hyper/hypothyroidism
• History of blood clotting abnormalities or platelet abnormalities
• History of chronic major psychiatric disorders or presence of current major depressive disorder (by DSM-IV criteria)
• History of substance abuse within the past year

Sponsors & Collaborators

• Seattle Institute for Biomedical and Clinical Research: lead

Study Sites (1)

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Related Publications (3)

• Li G, Larson EB, Sonnen JA, Shofer JB, Petrie EC, Schantz A, Peskind ER, Raskind MA, Breitner JC, Montine TJ. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology. 2007 Aug 28;69(9):878-85. doi: 10.1212/01.wnl.0000277657.95487.1c.

  PMID: 17724290 BACKGROUND

• Li G, Higdon R, Kukull WA, Peskind E, Van Valen Moore K, Tsuang D, van Belle G, McCormick W, Bowen JD, Teri L, Schellenberg GD, Larson EB. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology. 2004 Nov 9;63(9):1624-8. doi: 10.1212/01.wnl.0000142963.90204.58.

  PMID: 15534246 BACKGROUND

• Riekse RG, Li G, Petrie EC, Leverenz JB, Vavrek D, Vuletic S, Albers JJ, Montine TJ, Lee VM, Lee M, Seubert P, Galasko D, Schellenberg GD, Hazzard WR, Peskind ER. Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid. J Alzheimers Dis. 2006 Dec;10(4):399-406. doi: 10.3233/jad-2006-10408.

  PMID: 17183151 RESULT

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid

Interventions

Simvastatin; Pravastatin; Atorvastatin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Elaine R Peskind, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 14, 2006
• First Posted: March 16, 2006
• Study Start: August 1, 2002
• Primary Completion: April 1, 2005
• Study Completion: April 1, 2005
• Last Updated: April 13, 2010

Record last verified: 2010-04

Locations

US (1)