Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
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|ClinicalTrials.gov Identifier: NCT00303277|
Recruitment Status : Completed
First Posted : March 16, 2006
Last Update Posted : April 13, 2010
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease Aging||Drug: simvastatin Drug: pravastatin||Phase 4|
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 lipophilicity of the statin will affect its ability to decrease Abeta. In addition, the proposal will determine statin effects on both peripheral and central inflammation and whether the lipophilicity of the statin will affect its ability to decrease inflammation. If it can be demonstrated that statins alter AD-associated biomarkers, this would have broad implications for the treatment and prevention of AD.
This study will be performed in 60 cognitively normal middle-aged and older persons with hypercholesterolemia (total cholesterol >200 and/or LDL>130), presumably persons that have a lipid-related increased risk of AD and in whom alterations of CSF Abeta can be interpreted.The differential effects of the two statins will be evaluated in a 12-week randomized treatment trial with 30 subjects in each group.
Prior to randomization and following 12 weeks of treatment with simvastatin or pravastatin, subjects will undergo CSF and blood collection. In the CSF, concentrations of Abeta 1-40, Abeta 1-42, soluble APP, tau, 24S-hydroxycholesterol, apoE, total cholesterol, F2-isoprostanes, glucose, protein, and cell count will be measured. In the blood, concentrations of total cholesterol, HDL, LDL, triglyceride, phospholipids, fatty acids, 24S-hydroxycholesterol, apoE, apoB, apoA1, Abeta 1-40, Abeta 1-42, F2-isoprostanes, C-reactive protein, fibrinogen, iron, homocysteine, and albumin will be measured. Plasma simvastatin and pravastatin concentrations will be measured at study completion. APOE genotyping will be performed.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Do HMG CoA Reductase Inhibitors Affect Abeta Levels?|
|Study Start Date :||August 2002|
|Primary Completion Date :||April 2005|
|Study Completion Date :||April 2005|
U.S. FDA Resources
Active Comparator: 1
simvastatin 40 mg tablets once per day for 12 weeks
Other Name: Zocor
Active Comparator: 2
pravastatin 80 mg tablets once per day for 12 weeks
Other Name: Lipitor
- CSF abeta levels [ Time Frame: baseline and 12 weeks ]
- CSF biomarkers [ Time Frame: baseline and 12 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00303277
|United States, Washington|
|VA Puget Sound Health Care System|
|Seattle, Washington, United States, 98108|
|Principal Investigator:||Elaine R Peskind, MD||University of Washington|