Clinical trial NCT00842920: Trial of Simvastatin in Amnestic Mild Cognitive Impairment (MCI) Patients
Official title: Randomized Controlled Trial of Simvastatin in Amnestic MCI Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Mild Cognitive Impairment
Keywords: amnestic MCI
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2009-02-12
Enrollment: 520
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Change in CDR-SOB at 24 months of treatment
timeFrame: 24 month
Secondary outcomes:
measure: Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score
timeFrame: 24 month
measure: Change in Free and Cued Selective Reminding Test (FCSRT) score
timeFrame: 24 month
measure: 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
timeFrame: 24 months
Other outcomes:
measure: Change in CDR-SOB at Long-Term Follow-Up
timeFrame: 2-11 years
Locations:
city: Berlin
country: Germany
facility: Department of Psychiatry and Psychotherapy, Charité-CBF
city: Bonn
country: Germany
facility: Department of Psychiatry and Psychotherapy, University Bonn
city: Erlangen
country: Germany
facility: Department of Psychiatry and Psychotherapy, University Erlangen
city: Frankfurt am Main
country: Germany
facility: Department of Psychiatry and Psychotherapy, Johann Wolfgang Goethe-University
city: Freiburg
country: Germany
facility: Center for Geriatrics and Gerontology, University Freiburg
city: Göttingen
country: Germany
facility: Department of Psychiatry and Psychotherapy, Medical University Goettingen
city: Halle
country: Germany
facility: Department for Psychiatry, Psychotherapy and Psychosomatic; Martin-Luther-University Halle-Wittenberg
city: Heidelberg
country: Germany
facility: Department of Psychiatry, University Hospital Heidelberg
city: Mannheim
country: Germany
facility: Department of Gerontopsychiatry, Central Institut of Mental Health, University Heidelberg
city: Munich
country: Germany
facility: Department of Psychiatry and Psychotherapy, LMU I
city: Munich
country: Germany
facility: Institute for Stroke and Dementia Research, LMU
city: Rostock
country: Germany
facility: Department of Psychiatry and Psychotherapy, University Rostock
city: Ulm
country: Germany
facility: Neurologische Universitätsklinik Ulm
Study officials:
affiliation: Charité-CBF
name: Isabella Heuser, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CIMH Mannheim
name: Lutz Frölich, MD
role: PRINCIPAL_INVESTIGATOR
References: