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

• ClinicalTrials.gov Identifier: NCT02719327
• Recruitment Status: Active, not recruiting
• First Posted: March 25, 2016
• Last Update Posted: October 10, 2022
• Sponsor: VA Office of Research and Development
• Collaborator: University of Wisconsin, Madison
• Information provided by (Responsible Party): VA Office of Research and Development

Tracking Information

• First Submitted Date: March 21, 2016
• First Posted Date: March 25, 2016
• Last Update Posted Date: October 10, 2022
• Actual Study Start Date: June 8, 2017
• Estimated Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: March 21, 2016): Regional cerebral blood flow using arterial spin-labeling MRI [ Time Frame: 18 months ]

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid
• Official Title: 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. 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: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

1:1 randomization of icosapent ethyl 4 g daily vs matching placebo

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention

• Condition: Alzheimer's Disease

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 6, 2022): 131
• Original Estimated Enrollment (submitted: March 21, 2016): 150
• Estimated Study Completion Date: September 29, 2023
• Estimated Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02719327
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: VA Office of Research and Development
• Original Responsible Party: Same as current
• Current Study Sponsor: VA Office of Research and Development
• Original Study Sponsor: Same as current
• Collaborators: University of Wisconsin, Madison

Investigators

• 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: October 2022