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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02719327
Recruitment Status : Recruiting
First Posted : March 25, 2016
Last Update Posted : April 15, 2020
Sponsor:
Collaborator:
University of Wisconsin, Madison
Information provided by (Responsible Party):
VA Office of Research and Development

Study Description
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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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: icosapent ethyl (IPE) Other: gel cap placebo Phase 2 Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of Icosapent Ethyl on Alzheimers Disease Biomarkers in Preclinical Adults
Actual Study Start Date : June 8, 2017
Estimated Primary Completion Date : November 30, 2021
Estimated Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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
 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
Placebo Comparator: placebo
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease [ Time Frame: 18 months ]
    CSF beta-amyloid, total tau, and phosphorylated tau

  2. cognitive performance [ Time Frame: 18 months ]
    Preclinical Alzheimer's Cognitive Composite (PACC)


Eligibility Criteria
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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02719327


Contacts
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Contact: Cynthia M Carlsson, MD MS (608) 280-7000 Cynthia.Carlsson@va.gov
Contact: Elena G Beckman (608) 256-1901 Elena.Beckman@va.gov

Locations
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United States, Wisconsin
William S. Middleton Memorial Veterans Hospital, Madison, WI Recruiting
Madison, Wisconsin, United States, 53705
Contact: Aaron F Heneghan, PhD    608-256-1901 ext 17801    Aaron.Heneghan@va.gov   
Contact: Nasia Safdar, MD PhD    (608) 280-7007    Nasia.Safdar@va.gov   
Principal Investigator: Cynthia M. Carlsson, MD MS         
Sponsors and Collaborators
VA Office of Research and Development
University of Wisconsin, Madison
Investigators
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Principal Investigator: Cynthia M. Carlsson, MD MS William S. Middleton Memorial Veterans Hospital, Madison, WI
More Information
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02719327    
Other Study ID Numbers: CLNA-001-15S
CX001261 ( Other Grant/Funding Number: VA Merit )
First Posted: March 25, 2016    Key Record Dates
Last Update Posted: April 15, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by VA Office of Research and Development:
Alzheimer's disease
Cerebrospinal fluid
brain blood flow
cognition
 icosapent ethyl
Vascepa
omega-3 fatty acids
eicosapentaenoic acid
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
 Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Eicosapentaenoic acid ethyl ester
Platelet Aggregation Inhibitors