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

Phase 4

• Conditions: Mild Cognitive Impairment
• Interventions: Drug: Simvastatin 60 mg; Drug: Simvastatin 20 mg; Drug: Placebo

• Registration Number: NCT00842920
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-12
• Study First Submitted: 2009-02-11
• Study First Submitted QC: 2009-02-11
• Study First Posted: 2009-02-12
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-22
• Last Update Posted: 2020-01-27
• Primary Completion: 2020-08-31
• Study Completion: 2021-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 520

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simvastatin 60 mg	Simvastatin 60 mg	Simvastatin 60 mg once daily
Simvastatin 20 mg	Simvastatin 20 mg	Simvastatin 20 mg once daily
Placebo	Placebo	Placebo or 20 mg Simvastatin (stratified by prior use of statins)

Primary Outcome Measures

Name	Time	Method
Change in CDR-SOB at 24 months of treatment	24 month	Clinical dementia rating - sum of boxes

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (13)

Department of Psychiatry and Psychotherapy, University Bonn; 🇩🇪 Bonn, Germany

Department of Psychiatry and Psychotherapy, Charité-CBF; 🇩🇪 Berlin, Germany

Department of Psychiatry and Psychotherapy, Johann Wolfgang Goethe-University; 🇩🇪 Frankfurt am Main, Germany

Center for Geriatrics and Gerontology, University Freiburg; 🇩🇪 Freiburg, Germany

Department of Psychiatry and Psychotherapy, University Erlangen; 🇩🇪 Erlangen, Germany

Department for Psychiatry, Psychotherapy and Psychosomatic; Martin-Luther-University Halle-Wittenberg; 🇩🇪 Halle, Germany

Department of Psychiatry and Psychotherapy, Medical University Goettingen; 🇩🇪 Göttingen, Germany

Department of Gerontopsychiatry, Central Institut of Mental Health, University Heidelberg; 🇩🇪 Mannheim, Germany

Department of Psychiatry, University Hospital Heidelberg; 🇩🇪 Heidelberg, Germany

Department of Psychiatry and Psychotherapy, LMU I; 🇩🇪 Munich, Germany

Institute for Stroke and Dementia Research, LMU; 🇩🇪 Munich, Germany

Department of Psychiatry and Psychotherapy, University Rostock; 🇩🇪 Rostock, Germany

Neurologische Universitätsklinik Ulm; 🇩🇪 Ulm, Germany