Trial of Simvastatin in Amnestic Mild Cognitive Impairment (MCI) Patients

Study Overview
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Brief Summary
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Probands with MCI are at high risk to develop Alzheimer´s dementia (AD). Simvastatin may lower the production of Amyloid, a hallmark of AD in the brain. The primary hypothesis of the study is that 60 mg Simvastatin significantly reduces the Clinical Dementia Rating -Sum of boxes (CDR-SOB) in individuals with MCI as compared to MCI receiving placebo or 20 mg Simvastatin

Detailed Description
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This is a national multicenter, double-blind, randomized placebo-controlled trial allowing for a minimum follow-up time of 24 months in conversion-free patients. Randomization will be stratified by prior use of statins. The two strata are: no-statins: patients without treatment with a statins and no indication for treatment (according to the guidelines of the German Society of Cardiology for the primary prevention of cardiovascular disease); patients will be randomly assigned to one of 2 treatment (1) Simvastatin (60 mg) one tablet/day (2) Placebo one tablet/day. low-statins: patients treated with low doses of Statins; patients will be randomly assigned to one of 2 treatment (1) Simvastatin (60 mg) one tablet/day (2) 20 mg Simvastatin one tablet/day.

Official Title
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Randomized Controlled Trial of Simvastatin in Amnestic MCI Patients

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Simvastatin 60 mg
* Drug: Placebo
* Drug: Simvastatin 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Self and informant report of gradually increasing memory impairment for at least six months. Objective memory impairment Intact basic activities of daily living Preserved general cognitive function, not demented Absence of a detectable cause of memory disorder Age 55 to 90. Females without childbearing potential A total cholesterol ≥90 mg/dl LDL-cholesterol ≥ 160 mg/dl and ≤ 3 risk factors or ≥ 190 mg/dl and ≤ 2 risk factors including age Informed consent (according german medicinal products act, AMG §40 (1) 3b) No participation in other clinical trials 2 months before and after participation in this study Probands should only recruited for the clinical trial, when they are able to perform the informed consent; due to worsening of memory function in the course of the clinical trial, probands should not longer participate the clinical trial, when they is evidence, that participants were not longer able to give full informed consent. Exclusion Criteria: Hypersensitivity against Simvastatin, active liver disease or lasting increase of serum transaminases for unclear reason Unstable medical, neurological or psychiatric disease Lack of a spouse or a close relative Use of a registered anti-dementia drug or a nootropic Chronic use of anti-inflammatory drugs History of stroke or myocardial infarction LDL-cholesterol 130-160 mg/dl and > 3 risk factors or 160-190 mg/dl and > 2 risk factors including age. LDL-cholesterol >190 mg/dl Comedication with Diltiazem, Verapamil, Amiodarone, Itraconazole, Ketoconazole, Erythromycin, Clarithromycin, Telithromycin, Ciclosporin, Gemfibrozil, Nefazodone, HIV-protease inhibitors, Benzodiazepines, Tricyclic antipsychotics or other anticholinergic drugs Comedication of other statins in high doses; low doses equivalent to 20 mg Simvastatin are allowed if taken for max. 2 years before randomization

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo or 20 mg Simvastatin (stratified by prior use of statins) | Drug: Placebo<br>* one tablet once daily<br>|
| Experimental: Simvastatin 60 mg<br>Simvastatin 60 mg once daily | Drug: Simvastatin 60 mg<br>* 60 mg once daily<br>|
| Experimental: Simvastatin 20 mg<br>Simvastatin 20 mg once daily | Drug: Simvastatin 20 mg<br>* 20 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CDR-SOB at 24 months of treatment | Clinical dementia rating - sum of boxes | 24 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score |  | 24 month | 
| Change in Free and Cued Selective Reminding Test (FCSRT) score |  | 24 month | 
| Length of conversion-free interval, starting at the time of randomization, with conversion being defined as an increase of the CDR score beyond 0.5 |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amnestic MCI