SIMaMCI: Prevention of Alzheimer´s dementia by administration of simvastati

Phase 1

• Conditions: Amnestic mild cognitive impairment (MCI) denotes clinical conditions in the border zone between normal cognitive functioning and dementia. The definition of amnestic MCI by Petersen and his co-workers is an attempt to focus on those MCI patients who are at greatest risk to develop Alzheimer´s disease. There has to be subjective and objective memory impairment, but general cognitive function and activities of daily living must be essentially intact.; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2008-002226-11-DE
• Lead Sponsor: Charité - Unversitätsmedizin Berlin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-09-03
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 520

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 85.
(7)Females without childbearing potential
(8)A total cholesterol =90 mg/dl
(9)LDL-cholesterol < 130 mg/dl. LDL-cholesterol 130-160 mg/dl = 3 risk factors including age or 160-190 mg/dl and =2 risk factors (only controlled hypertension and age);
(10) Informed consent (according AMG §40 (1) 3b)
(11) No participation in other clinical trials 2 months before and after participation in this study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 370

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. LDL-cholesterol >190 mg/dl
(8) Comedication with Diltiazem, Verapamil, Amiodaron, Itraconazol, Ketokonazol, Erythromycin, Clarithromycin, Telithromycin, Ciclosporin, Gemfibrozil, Nefazodon, HIV-protease inhibitors, benzodiazepines, tricyclic antipsychotics or other anticholinergic drugs; co-medication of statins in high doses; low doses equivalent to 20 mg Simvastatin are allowed if taken for max. 2 years before randomization
(9) Persons who are detained officially or legally to an official institute

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Simvastatin significantly reduces the conversion rate to Alzheimer’s dementia in probands with MCI as compared to MCI receiving placebo;Secondary Objective: 1) The benefit from simvastatin treatment is larger in probands with a low level of ß-amyloid (Aß42 530ng/l; Aß40 5612 ng/l) / increased level of Tau (t-Tau 350 ng/l; p-Tau 60 ng/l) in CSF as compared to patients above/below the respective cut-off values. <br>(2)The benefit from simvastatin treatment is larger in APO-E4 allele carriers than in other APO-E allele individuals;Primary end point(s): Prevention of conversion to Alzheimer’s dementia in probands with amnestic MCI by administration of simvastatin. Primary efficacy endpoint: Change in CDR-SOB at 24 months of Treatment. <br>;Timepoint(s) of evaluation of this end point: 24 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Change in ADAS-Cog and FCSRT score<br>2) Length of conversion-free Intervall, starting at the time of randomization, with conversion being defined as an increase of the CDR-Score beyond 0.5<br>3) Change in ADCS-ADL score<br>4) Change in volumetric brain measures (structural MRI)<br>5) Change in CSF and blood measures of beta-amyloid peptides, total and phosphorylized TAU Proteins and measures of cerebral cholesterol metabolites<br>6) Impact on cost efficacy Ratio (ICER)<br>7) Pharmacogenetic prediction parameters;Timepoint(s) of evaluation of this end point: Time to AD conversion will be tested by means of a log-rank test for differences between two survival functions.