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

Randomized Controlled Trial of Simvastatin in Amnestic MCI Patients

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

Study Overview

• Status: Unknown
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Drug: Placebo; Drug: Simvastatin 60 mg; Drug: Simvastatin 20 mg

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 Type: Interventional
• Enrollment (Anticipated): 520
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Department of Psychiatry and Psychotherapy, Charité-CBF
  • Bonn, Germany, 53105
    • Department of Psychiatry and Psychotherapy, University Bonn
  • Erlangen, Germany, 91054
    • Department of Psychiatry and Psychotherapy, University Erlangen
  • Frankfurt am Main, Germany, 60528
    • Department of Psychiatry and Psychotherapy, Johann Wolfgang Goethe-University
  • Freiburg, Germany, 79106
    • Center for Geriatrics and Gerontology, University Freiburg
  • Göttingen, Germany, 37075
    • Department of Psychiatry and Psychotherapy, Medical University Goettingen
  • Halle, Germany, 06112
    • Department for Psychiatry, Psychotherapy and Psychosomatic; Martin-Luther-University Halle-Wittenberg
  • Heidelberg, Germany, 69115
    • Department of Psychiatry, University Hospital Heidelberg
  • Mannheim, Germany, 68072
    • Department of Gerontopsychiatry, Central Institut of Mental Health, University Heidelberg
  • Munich, Germany, 80336
    • Department of Psychiatry and Psychotherapy, LMU I
  • Munich, Germany, 81377
    • Institute for Stroke and Dementia Research, LMU
  • Rostock, Germany
    • Department of Psychiatry and Psychotherapy, University Rostock
  • Ulm, Germany, 89081
    • Neurologische Universitätsklinik Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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	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

Other Outcome Measures

Outcome Measure	Time Frame
Change in CDR-SOB at Long-Term Follow-Up	2-11 years

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Principal Investigator: Isabella Heuser, MD, PhD, Charité-CBF; Principal Investigator: Lutz Frölich, MD, CIMH Mannheim

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2008
• Primary Completion (Anticipated): August 31, 2020
• Study Completion (Anticipated): February 28, 2021

Study Registration Dates

• First Submitted: February 11, 2009
• First Submitted That Met QC Criteria: February 11, 2009
• First Posted (Estimate): February 12, 2009

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: amnestic MCI
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: EudraCT 2008-002226-11; BMBF grant, 01KG0822