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

Mild Cognitive Impairment Clinical Trial

— SIMaMCI  

Official title:

Randomized Controlled Trial of Simvastatin in Amnestic MCI Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00842920
• Other study ID #: EudraCT 2008-002226-11
• Secondary ID: BMBF grant, 01KG
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 2008
• Est. completion date: February 28, 2021

Study information

• Verified date: January 2020
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 520
• Est. completion date: February 28, 2021
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Drug:
• Simvastatin 60 mg
60 mg once daily
• Placebo
one tablet once daily
• Simvastatin 20 mg
20 mg once daily

Locations

Country	Name	City	State
Germany	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
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

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in CDR-SOB at Long-Term Follow-Up		2-11 years
Primary	Change in CDR-SOB at 24 months of treatment	Clinical dementia rating - sum of boxes	24 month
Secondary	Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score		24 month
Secondary	Change in Free and Cued Selective Reminding Test (FCSRT) score		24 month
Secondary	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