Trial of Simvastatin in Amnestic Mild Cognitive Impairment (MCI) Patients - Full Text View

Purpose

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

Condition	Intervention	Phase
Mild Cognitive Impairment	Drug: Simvastatin Drug: Placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Randomized Controlled Trial of Simvastatin in Amnestic MCI Patients

Resource links provided by NLM:

MedlinePlus related topics: Mild Cognitive Impairment

Drug Information available for: Simvastatin

U.S. FDA Resources

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

Change in CDR-SOB at 24 months of treatment [ Time Frame: 24 month ] [ Designated as safety issue: No ]
Clinical dementia rating - sum of boxes

Secondary Outcome Measures:

Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score [ Time Frame: 24 month ] [ Designated as safety issue: No ]
Change in Free and Cued Selective Reminding Test (FCSRT) score [ Time Frame: 24 month ] [ Designated as safety issue: No ]
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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]


Estimated Enrollment:	520
Study Start Date:	December 2008
Estimated Study Completion Date:	March 2019
Estimated Primary Completion Date:	October 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Placebo or 20 mg Simvastatin (stratified by prior use of statins)	Drug: Placebo one tablet once daily
Experimental: Simvastatin Simvastatin 60 mg once daily	Drug: Simvastatin 60 mg once daily

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:

"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.
"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


Ages Eligible for Study:	55 Years to 90 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Self and informant report of gradually increasing memory impairment for at least six months.
Objective memory impairment
Intact basic activities of daily living
Preserved general cognitive function, not demented
Absence of a detectable cause of memory disorder
Age 55 to 90.
Females without childbearing potential
A total cholesterol ≥90 mg/dl
LDL-cholesterol ≥ 160 mg/dl and ≤ 3 risk factors or ≥ 190 mg/dl and ≤ 2 risk factors including age
Informed consent (according german medicinal products act, AMG §40 (1) 3b)
No participation in other clinical trials 2 months before and after participation in this study
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:

Hypersensitivity against Simvastatin, active liver disease or lasting increase of serum transaminases for unclear reason
Unstable medical, neurological or psychiatric disease
Lack of a spouse or a close relative
Use of a registered anti-dementia drug or a nootropic
Chronic use of anti-inflammatory drugs
History of stroke or myocardial infarction
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
Comedication with Diltiazem, Verapamil, Amiodarone, Itraconazole, Ketoconazole, Erythromycin, Clarithromycin, Telithromycin, Ciclosporin, Gemfibrozil, Nefazodone, HIV-protease inhibitors, Benzodiazepines, Tricyclic antipsychotics or other anticholinergic drugs
Comedication of other statins in high doses; low doses equivalent to 20 mg Simvastatin are allowed if taken for max. 2 years before randomization

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00842920

Locations


Germany
Department of Neurology, Charité-CBF	Recruiting
Berlin, Germany, 12200
Contact: Joachim Weber, MD +49308445 ext 4705 joachim.weber@charite.de
Principal Investigator: Joachim Weber, MD
Department of Psychiatry and Psychotherapy, Charité-CBF	Recruiting
Berlin, Germany
Contact: Oliver Peters, MD +49-30-8445-8215 oliver.peters@charite.de
Sub-Investigator: Oliver Peters, MD
Principal Investigator: Isabella Heuser, MD
Department of Psychiatry and Psychotherapy, University Bonn	Recruiting
Bonn, Germany, 53105
Contact: Wolfgang Maier, Prof w.maier@uni-bonn.de
Principal Investigator: Wolfgang Maier, MD
Department of Psychiatry and Psychotherapy, University Erlangen	Recruiting
Erlangen, Germany, 91054
Contact: Kornhuber Johannes, MD 09131/85 ext 34166 johanneskornhuber@uk-erlangen.de
Principal Investigator: Johannes Kornhuber, MD
Department of Psychiatry and Psychotherapy, Johann Wolfgang Goethe-University	Recruiting
Frankfurt am Main, Germany, 60528
Contact: Tarik Karakaya, MD +49 69 6301 ext 5259 tarik.karakaya@kgu.de
Principal Investigator: Tarik Karakaya, MD
Center for Geriatrics and Gerontology, University Freiburg	Recruiting
Freiburg, Germany, 79106
Contact: Stefan Klöppel, MD stefan.kloeppel@uniklinik-freiburg.de
Principal Investigator: Stefan Klöppel, MD
Department of Psychiatry and Psychotherapy, Medical University Goettingen	Recruiting
Goettingen, Germany, 37075
Contact: Anja Schneider, MD 0551-3914258 aschnei8@gwdg.de
Principal Investigator: Anja Schneider, MD
Department for Psychiatry, Psychotherapy and Psychosomatic; Martin-Luther-University Halle-Wittenberg	Active, not recruiting
Halle, Germany, 06112
Department of Psychiatry, University Hospital Heidelberg	Recruiting
Heidelberg, Germany, 69115
Contact: Johannes Schröder, MD johannes_schroeder@med.uni-heidelberg.de
Principal Investigator: Johannes Schröder, MD
Department of Gerontopsychiatry, Central Institut of Mental Health, University Heidelberg	Recruiting
Mannheim, Germany, 68072
Contact: Lutz Fröhlich, MD +49 621 1703 ext 3001 lutz.froelich@zi-mannheim.de
Principal Investigator: Lutz Fröhlich, MD
Department of Neurology, Philipps University Marburg	Recruiting
Marburg, Germany, 35032
Contact: Richard Dodel, MD richard.dodel@staff.uni-marburg.de
Principal Investigator: Richard Dodel, MD
Department of Psychiatry and Psychotherapy, LMU I	Recruiting
Munich, Germany, 80336
Contact: Eva Meisenzahl, MD 089-5160 ext 5772 eva.meisenzahl@med.uni-muenchen.de
Principal Investigator: Eva Meisenzahl, MD
Institute for Stroke and Dementia Research, LMU	Recruiting
Munich, Germany, 81377
Contact: Katharina Bürger, MD +49-89-7095 ext 8330 katharina.buerger@med.uni-muenchen.de
Principal Investigator: Katharina Bürger, MD
Department of Psychiatry and Psychotherapy, University Rostock	Recruiting
Rostock, Germany
Contact: Stefan Teipel, MD +49-381-494-9610 stefan.teipel@med.uni-rostock.de
Principal Investigator: Stefan Teipel, MD
Neurologische Universitätsklinik Ulm	Recruiting
Ulm, Germany, 89081
Contact: Christine von Arnim, MD +49-731- ext 177-5201 christine.arnim@uni-ulm.de
Principal Investigator: Christine von Arnim, MD

Sponsors and Collaborators

Charite University, Berlin, Germany

German Federal Ministry of Education and Research

Investigators


Principal Investigator:	Isabella Heuser, MD, PhD	Charité-CBF
Principal Investigator:	Lutz Frölich, MD	CIMH Mannheim

More Information


Responsible Party:	Isabella Heuser, Prof. Dr., Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00842920 History of Changes
Other Study ID Numbers:	EudraCT 2008-002226-11 BMBF grant, 01KG0822
Study First Received:	February 11, 2009
Last Updated:	September 15, 2015
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:


amnestic MCI

Additional relevant MeSH terms:


Cognition Disorders Mild Cognitive Impairment Neurocognitive Disorders Mental Disorders Simvastatin Anticholesteremic Agents	Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016

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