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

Charité University Medicine Berlin

Status and phase: Unknown; Phase 4

Conditions: Mild Cognitive Impairment

Treatments: Drug: Simvastatin 20 mg; Drug: Placebo; Drug: Simvastatin 60 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT00842920

EudraCT 2008-002226-11

BMBF grant, 01KG0822

Details and patient eligibility

About

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

Full description

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:

1. "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.
2. "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.

Enrollment: 520 estimated patients

Sex: All

Ages: 55 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Self and informant report of gradually increasing memory impairment for at least six months.
2. Objective memory impairment
3. Intact basic activities of daily living
4. Preserved general cognitive function, not demented
5. Absence of a detectable cause of memory disorder
6. Age 55 to 90.
7. Females without childbearing potential
8. A total cholesterol ≥90 mg/dl
9. LDL-cholesterol ≥ 160 mg/dl and ≤ 3 risk factors or ≥ 190 mg/dl and ≤ 2 risk factors including age
10. Informed consent (according german medicinal products act, AMG §40 (1) 3b)
11. No participation in other clinical trials 2 months before and after participation in this study
12. 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

1. Hypersensitivity against Simvastatin, active liver disease or lasting increase of serum transaminases for unclear reason
2. Unstable medical, neurological or psychiatric disease
3. Lack of a spouse or a close relative
4. Use of a registered anti-dementia drug or a nootropic
5. Chronic use of anti-inflammatory drugs
6. History of stroke or myocardial infarction
7. LDL-cholesterol 130-160 mg/dl and > 3 risk factors or 160-190 mg/dl and > 2 risk factors including age.
8. LDL-cholesterol >190 mg/dl
9. Comedication with Diltiazem, Verapamil, Amiodarone, Itraconazole, Ketoconazole, Erythromycin, Clarithromycin, Telithromycin, Ciclosporin, Gemfibrozil, Nefazodone, HIV-protease inhibitors, Benzodiazepines, Tricyclic antipsychotics or other anticholinergic drugs
10. Comedication of other statins in high doses; low doses equivalent to 20 mg Simvastatin are allowed if taken for max. 2 years before randomization

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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520 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo or 20 mg Simvastatin (stratified by prior use of statins)

Treatment:

Drug: Placebo

Simvastatin 60 mg

Experimental group

Description:

Simvastatin 60 mg once daily

Treatment:

Drug: Simvastatin 60 mg

Simvastatin 20 mg

Experimental group

Description:

Simvastatin 20 mg once daily

Treatment:

Drug: Simvastatin 20 mg