Mild Cognitive Impairment
Conditions
Keywords
amnestic MCI
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.
Interventions
DRUGSimvastatin 60 mg
60 mg once daily
DRUGPlacebo
one tablet once daily
20 mg once daily
Sponsors
German Federal Ministry of Education and Research
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CDR-SOB at 24 months of treatment | 24 month | Clinical dementia rating - sum of boxes |
Secondary
| 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
| Measure | Time frame |
|---|---|
| Change in CDR-SOB at Long-Term Follow-Up | 2-11 years |
Countries
Germany
Outcome results
None listed