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Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid (BRAVE-EPA)

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ClinicalTrials.gov Identifier: NCT02719327
Recruitment Status : Recruiting
First Posted : March 25, 2016
Last Update Posted : April 17, 2019
Sponsor:
Collaborator:
University of Wisconsin, Madison
Information provided by (Responsible Party):
VA Office of Research and Development

Tracking Information
First Submitted Date  ICMJE March 21, 2016
First Posted Date  ICMJE March 25, 2016
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE June 8, 2017
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2017)
Regional cerebral blood flow using arterial spin-labeling MRI [ Time Frame: 18 months ]
Brain blood flow in a statistical region of interest will be measured through arterial spin-labeling MRI
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2016)
Regional cerebral blood flow using arterial spin-labeling MRI [ Time Frame: 18 months ]
Change History Complete list of historical versions of study NCT02719327 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2016)
  • Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease [ Time Frame: 18 months ]
    CSF beta-amyloid, total tau, and phosphorylated tau
  • cognitive performance [ Time Frame: 18 months ]
    Preclinical Alzheimer's Cognitive Composite (PACC)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid
Official Title  ICMJE Impact of Icosapent Ethyl on Alzheimers Disease Biomarkers in Preclinical Adults
Brief Summary The number of Americans diagnosed with Alzheimer's disease (AD) is expected to triple by 2050. Compared to the general population, Veterans have a greater risk of AD, likely in part due to their increased incidence of traumatic brain injury, post-traumatic stress disorder, depression, and other vascular-related health issues. Based on available data, 423,000 new cases of AD are anticipated in Veterans by 2020. Thus, the discovery of effective therapies to prevent or delay the onset of AD in Veterans is critical. The goal of this study is to evaluate the efficacy of a purified form of the omega-3 fatty acid eicosapentaenoic acid (EPA) called icosapent ethyl (IPE), on improving brain blood flow, spinal fluid markers of AD pathology, and cognitive performance in middle-aged, cognitively-healthy Veterans with increased risk of AD. If IPE delays the onset of AD by even 5 years, the incidence of AD would be reduced by 50% in this population and could have a profound effect on Veteran quality of life and healthcare costs.
Detailed Description The proposed study is a proof-of-concept, randomized, placebo-controlled, double-blind, parallel-group clinical trial assessing the efficacy of 18 months of icosapent ethyl (IPE) therapy on magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and cognitive biomarkers for AD in 150 cognitively-healthy Veterans ages 50-75 years with increased risk for developing AD due to parental history of the disease and increased prevalence of apolipoprotein E4 (APOE4) allele. The overarching goal of this trial is to assess whether icosapent ethyl beneficially affects intermediate physiological measures associated with onset of AD in order to evaluate whether larger, multi-site, longer-duration Alzheimer's prevention trials are warranted to assess more definitive clinical outcomes. The proposed study aims to: 1) investigate the effects of 18 months of IPE vs. placebo on regional cerebral blood flow as measured by arterial spin-labeling MRI; 2) determine the impact of 18 months of IPE vs. placebo on CSF biomarkers of AD pathology; and 3) evaluate the effects of 18 months of IPE vs. placebo on cognitive performance.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: icosapent ethyl (IPE)
    Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
    Other Name: Vascepa
  • Other: gel cap placebo
    Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: icosapent ethyl (IPE)
    Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
    Intervention: Drug: icosapent ethyl (IPE)
  • Placebo Comparator: placebo
    Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
    Intervention: Other: gel cap placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 21, 2016)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2021
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Parental history of Alzheimer's disease
  • United States Veteran eligible for VA care
  • Age 50-75 years, inclusive
  • Cognitively healthy

Exclusion Criteria:

  • Dementia or mild cognitive impairment on screening evaluation
  • Current use of fish oil supplements (requires 3 month wash-out period)
  • Active liver disease with AST or ALT greater than twice the upper limit of normal
  • Elevated creatine kinase greater than twice the upper limit of normal
  • Prior adverse reaction to statins or fish oil
  • Pregnant, nursing, or pregnancy planned
  • Use of medications that interact with icosapent ethyl
  • Current use of anticoagulants
  • Known hypersensitivity to fish and/or shellfish
  • Current use of other investigational drug
  • History of significant atherosclerotic cardiovascular disease or diabetes mellitus
  • Low-density lipoprotein (LDL) cholesterol > or =190 mg/dL or <80 mg/dL
  • Triglycerides > or = 500 mg/dL
  • Creatinine >1.8 mg/dL
  • Previous lumbar surgery with contraindication to lumbar puncture
  • Claustrophobia requiring sedation for MRI
  • Pacemaker or other contraindication for MRI
  • Consumption of >200 mg per day omega-3 fatty acids in diet
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Cynthia M Carlsson, MD MS (608) 280-7000 Cynthia.Carlsson@va.gov
Contact: Elena G Beckman (608) 256-1901 Elena.Beckman@va.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02719327
Other Study ID Numbers  ICMJE CLNA-001-15S
CX001261 ( Other Grant/Funding Number: VA Merit )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party VA Office of Research and Development
Study Sponsor  ICMJE VA Office of Research and Development
Collaborators  ICMJE University of Wisconsin, Madison
Investigators  ICMJE
Principal Investigator: Cynthia M. Carlsson, MD MS William S. Middleton Memorial Veterans Hospital, Madison, WI
PRS Account VA Office of Research and Development
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP