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Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
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Purpose
| Condition | Intervention | Phase |
|---|---|---|
| Alzheimer's Disease Aging | Drug: simvastatin Drug: pravastatin | Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Prevention |
| Official Title: | Do HMG CoA Reductase Inhibitors Affect Abeta Levels? |
- CSF abeta levels [ Time Frame: baseline and 12 weeks ]
- CSF biomarkers [ Time Frame: baseline and 12 weeks ]
| Enrollment: | 35 |
| Study Start Date: | August 2002 |
| Study Completion Date: | April 2005 |
| Primary Completion Date: | April 2005 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
simvastatin
|
Drug: simvastatin
simvastatin 40 mg tablets once per day for 12 weeks
Other Name: Zocor
|
|
Active Comparator: 2
pravastatin
|
Drug: pravastatin
pravastatin 80 mg tablets once per day for 12 weeks
Other Name: Lipitor
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years to 90 Years (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00303277
| United States, Washington | |
| VA Puget Sound Health Care System | |
| Seattle, Washington, United States, 98108 | |
| Principal Investigator: | Elaine R Peskind, MD | University of Washington |
More Information
Publications:
| Responsible Party: | Elaine R. Peskind, MD, Professor, Director of Clinical Research, Mental Health Service, VA Puget Sound Health Care System/University of Washington School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00303277 History of Changes |
| Other Study ID Numbers: |
21974 |
| Study First Received: | March 14, 2006 |
| Last Updated: | April 12, 2010 |
Keywords provided by Seattle Institute for Biomedical and Clinical Research:
|
Alzheimer's disease beta-amyloid statins |
Additional relevant MeSH terms:
|
Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |
Simvastatin Pravastatin Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 23, 2017