SIMaMCI: prevention of Alzheimer´s dementia by administration of simvastatin

INTERVENTION: Trade Name: SimvaHexal Product Name: Simvastatin Pharmaceutical Form: Capsule, hard INN or Proposed INN: Simvastatin CAS Number: 79902‐63‐9 Current Sponsor code: Simvastatin Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 60‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Simvahexal Product Name: Simvastatin Pharmaceutical Form: Capsule, hard CONDITION: 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] PRIMARY OUTCOME: Main Objective: Simvastatin significantly reduces the conversion rate to Alzheimer’s dementia in probands with MCI as compared to MCI receiving placebo 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. ; 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. ; (2)The benefit from simvastatin treatment is larger in APO‐E4 allele carriers than in other APO‐E allele individuals Timepoint(s) of evaluation of this end point: 24 months SECONDARY OUTCOME: Secondary end point(s): 1) Change in ADAS‐Cog and FCSRT score ; 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 ; 3) Change in ADCS‐ADL score ; 4) Change in volumetric brain measures (structural MRI) ; 5) Change in CSF and blood measures of beta‐amyloid peptides, total and phosphorylized TAU Proteins and measures of cerebral cholesterol metabolites ; 6) Impact on cost efficacy Ratio (ICER) ; 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. 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