Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
關鍵詞
抽象
描述
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.
日期
| 最後驗證: | 03/31/2010 |
| 首次提交: | 03/13/2006 |
| 提交的預估入學人數: | 03/13/2006 |
| 首次發布: | 03/15/2006 |
| 上次提交的更新: | 04/11/2010 |
| 最近更新發布: | 04/12/2010 |
| 實際學習開始日期: | 07/31/2002 |
| 預計主要完成日期: | 03/31/2005 |
| 預計完成日期: | 03/31/2005 |
狀況或疾病
干預/治療
Drug: 1
Drug: 2
相
手臂組
| 臂 | 干預/治療 |
|---|---|
| Active Comparator: 1 simvastatin | Drug: 1 simvastatin 40 mg tablets once per day for 12 weeks |
| Active Comparator: 2 pravastatin | Drug: 2 pravastatin 80 mg tablets once per day for 12 weeks |
資格標準
| 有資格學習的年齡 | 18 Years 至 18 Years |
| 有資格學習的性別 | All |
| 接受健康志願者 | 是 |
| 標準 | Inclusion Criteria: - 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 Exclusion Criteria: - 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 - Taking exclusionary medications |
結果
主要結果指標
1. CSF abeta levels [baseline and 12 weeks]
次要成果指標
1. CSF biomarkers [baseline and 12 weeks]
