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

NCT ID: NCT00842920

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 520 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2021-02-28

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.

Conditions

Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

one tablet once daily

Simvastatin 60 mg

Simvastatin 60 mg once daily

Group Type: EXPERIMENTAL

Simvastatin 60 mg

Intervention Type: DRUG

60 mg once daily

Simvastatin 20 mg

Simvastatin 20 mg once daily

Group Type: EXPERIMENTAL

Simvastatin 20 mg

Intervention Type: DRUG

20 mg once daily

Interventions

Simvastatin 60 mg

60 mg once daily

Intervention Type: DRUG

Placebo

one tablet once daily

Intervention Type: DRUG

Simvastatin 20 mg

20 mg once daily

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Isabella Heuser

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Isabella Heuser, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Charité-CBF

Lutz Frölich, MD

Role: PRINCIPAL_INVESTIGATOR

CIMH Mannheim

Locations

Department of Psychiatry and Psychotherapy, Charité-CBF

Berlin, , Germany

Department of Psychiatry and Psychotherapy, University Bonn

Bonn, , Germany

Department of Psychiatry and Psychotherapy, University Erlangen

Erlangen, , Germany

Department of Psychiatry and Psychotherapy, Johann Wolfgang Goethe-University

Frankfurt am Main, , Germany

Center for Geriatrics and Gerontology, University Freiburg

Freiburg im Breisgau, , Germany

Department of Psychiatry and Psychotherapy, Medical University Goettingen

Göttingen, , Germany

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

Halle, , Germany

Department of Psychiatry, University Hospital Heidelberg

Heidelberg, , Germany

Department of Gerontopsychiatry, Central Institut of Mental Health, University Heidelberg

Mannheim, , 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

Countries

Germany

Other Identifiers

BMBF grant, 01KG0822

Identifier Type: -

Identifier Source: secondary_id

EudraCT 2008-002226-11

Identifier Type: -

Identifier Source: org_study_id