Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00486044
Recruitment Status : Completed
First Posted : June 13, 2007
Results First Posted : November 5, 2015
Last Update Posted : November 5, 2015
National Institute on Aging (NIA)
Paul Beeson Faculty Scholars Program
The John A. Hartford Foundation
The Atlantic Philanthropies
Starr Foundation
American Federation for Aging Research
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Wisconsin, Madison

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Alzheimer Disease
Interventions: Drug: Simvastatin
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Middle-aged adults with parental history of Alzheimer's disease were recruited for this single-site trial (Madison, Wisconsin) from the Wisconsin Registry for Alzheimer's Prevention (WRAP) or the community through newsletters, websites, educational talks, health fairs, local clinics, and newspaper and magazine advertisements.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
103 participants enrolled in the trial and 100 were randomized to treatment (1 no longer met inclusion criteria, 2 declined participation).

Reporting Groups
Simvastatin Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months
Placebo Matching placebo tablet nightly for 9 months

Participant Flow:   Overall Study
    Simvastatin   Placebo
STARTED   51 [1]   49 [2] 
COMPLETED   49 [3]   46 [4] 
Withdrawal by Subject                2                1 
Adverse Event                0                1 
Lost to Follow-up                0                1 
[1] 50 received assigned intervention (1 withdrew during baseline) 27 in MRI sub-study
[2] 23 in MRI sub-study
[3] 27 completed MRI sub-study
[4] 21 completed MRI sub-study

  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
Simvastatin Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months
Placebo Matching placebo tablet nightly for 9 months
Total Total of all reporting groups

Baseline Measures
   Simvastatin   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 51   49   100 
[Units: Participants]
<=18 years   0   0   0 
Between 18 and 65 years   49   42   91 
>=65 years   2   7   9 
[Units: Years]
Mean (Standard Deviation)
 53.3  (7.4)   52.4  (8.5)   52.8  (8.0) 
[Units: Participants]
Female   35   35   70 
Male   16   14   30 
Region of Enrollment 
[Units: Participants]
United States   51   49   100 
[Units: Years]
Mean (Standard Deviation)
 16.1  (2.)   16.3  (3.2)   16.2  (2.9) 
Mini Mental State Exam [1] 
[Units: Points]
Mean (Standard Deviation)
 29.5  (0.8)   29.6  (0.6)   29.5  (0.7) 
[1] 0-30 points score range where higher scores represent better outcomes; <24 points indicate cognitive dysfunction.
Apolipoprotein E4 carrier [1] 
[Units: Participants]
 21   17   38 
[1] Apolipoprotein E4 is a genetic risk factor for Alzheimer's disease, which increases your risk of developing Alzheimer's disease by 2-10 fold depending on if you're a carrier of the allele.
Total cholesterol [1] 
[Units: mg/dL]
Mean (Standard Deviation)
 192.8  (36.4)   187.6  (27.7)   190.3  (32.4) 
[1] Measured by nuclear magnetic resonance (NMR) spectroscopy
High-sensitivity c-reactive protein 
[Units: mg/L]
Mean (Standard Deviation)
 2.59  (3.71)   2.03  (2.21)   2.32  (3.06) 
Cerebrospinal fluid beta-amyloid-42 [1] 
[Units: ng/L]
Mean (Standard Deviation)
 345.6  (77.1)   331.0  (83.7)   338.7  (80.2) 
[1] Primary outcome measured by xMAP; secondary analyses included measurement by Triplex method as well.

  Outcome Measures

1.  Primary:   Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42   [ Time Frame: baseline and 9 months ]

2.  Secondary:   Changes in Regional Cerebral Blood Flow on MRI   [ Time Frame: baseline and 9 months ]

3.  Secondary:   Change in Inflammatory Markers   [ Time Frame: baseline and 9 months ]

4.  Secondary:   Changes in Cognitive Performance   [ Time Frame: Baseline and 9 months ]

  Serious Adverse Events

  Other Adverse Events

  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact:  
Name/Title: Cynthia M. Carlsson, MD, MS
Organization: University of Wisconsin School of Medicine and Public Health
phone: 608-280-7000


Responsible Party: University of Wisconsin, Madison Identifier: NCT00486044     History of Changes
Other Study ID Numbers: IA0116
1K23AG026752-01 ( U.S. NIH Grant/Contract )
First Submitted: June 12, 2007
First Posted: June 13, 2007
Results First Submitted: November 16, 2012
Results First Posted: November 5, 2015
Last Update Posted: November 5, 2015