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Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00486044
First received: June 12, 2007
Last updated: October 1, 2015
Last verified: March 2014
Results First Received: November 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Alzheimer Disease
Interventions: Drug: Simvastatin
Drug: Placebo

  Participant Flow
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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
  Description
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] 
NOT COMPLETED   2   3 
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
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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
  Description
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 
Age 
[Units: Participants]
     
<=18 years   0   0   0 
Between 18 and 65 years   49   42   91 
>=65 years   2   7   9 
Age 
[Units: Years]
Mean (Standard Deviation)
 53.3  (7.4)   52.4  (8.5)   52.8  (8.0) 
Gender 
[Units: Participants]
     
Female   35   35   70 
Male   16   14   30 
Region of Enrollment 
[Units: Participants]
     
United States   51   49   100 
Education 
[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
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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
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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
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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
e-mail: cmc@medicine.wisc.edu


Publications:

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00486044     History of Changes
Other Study ID Numbers: IA0116
1K23AG026752-01 ( US NIH Grant/Contract Award Number )
Study First Received: June 12, 2007
Results First Received: November 16, 2012
Last Updated: October 1, 2015
Health Authority: United States: Federal Government