Icosapent Ethyl for Alzheimer's Disease

(BRAVE-EPA Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: VA Office of Research and Development

Must not be taking: Anticoagulants, Fish oil, others

Disqualifiers: Dementia, Diabetes, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether icosapent ethyl (IPE), a purified omega-3 fatty acid, can improve brain blood flow and cognitive performance in Veterans at risk for Alzheimer's disease (AD). Researchers aim for IPE to delay the onset of AD, significantly reducing its impact on Veterans' quality of life and healthcare costs. Participants will receive either IPE or a placebo (inactive substance) to compare results. Ideal participants are U.S. Veterans who are cognitively healthy but have an increased risk of developing AD. As a Phase 2 trial, this research measures how well IPE works in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires a 3-month period without fish oil supplements before participating. Additionally, you cannot use medications that interact with icosapent ethyl or anticoagulants. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that icosapent ethyl (IPE) is likely to be safe for humans?

Research has shown that icosapent ethyl (IPE) is generally safe and well-tolerated. In various studies, including those in real-world settings, most people taking IPE did not experience serious side effects. For example, one study found that participants managed the treatment well without major issues. Additionally, the FDA has approved IPE for reducing heart problems, indicating a recognized safety record. While no treatment is completely risk-free, the evidence so far suggests that IPE is safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard treatments for brain amyloid and vascular conditions, which often involve medications like cholinesterase inhibitors and memantine, icosapent ethyl (IPE) is derived from eicosapentaenoic acid, a type of omega-3 fatty acid. Researchers are excited about IPE because it targets inflammation and oxidative stress in the brain, which are believed to contribute to amyloid plaque formation and vascular issues. This unique mechanism of action could potentially offer a new way to address these conditions, providing benefits beyond what current treatments offer.

What evidence suggests that icosapent ethyl (IPE) might be an effective treatment for Alzheimer's disease?

Research has shown that icosapent ethyl (IPE) may reduce heart problems, such as heart attacks, in individuals with high triglyceride levels who are already on statins. This is significant because heart health closely relates to brain health, particularly in conditions like Alzheimer's disease. Although IPE has primarily been studied for heart issues, it might also benefit brain health by enhancing blood flow. Early findings suggest that improved blood flow could delay or reduce the risk of Alzheimer's disease. In this trial, participants will receive either IPE or a placebo to determine if IPE can enhance brain function and delay Alzheimer's in high-risk groups, such as Veterans. ^{2 6 7 8 9}

Who Is on the Research Team?

Cynthia M. Carlsson, MD MS

Principal Investigator

William S. Middleton Memorial Veterans Hospital, Madison, WI

Are You a Good Fit for This Trial?

Inclusion Criteria

United States Veteran eligible for VA care

Age 50-75 years, inclusive

You should not have any significant problems with thinking, memory, or decision-making abilities.

Exclusion Criteria

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive icosapent ethyl or placebo for 18 months to assess effects on brain blood flow, CSF biomarkers, and cognitive performance

18 months

Regular visits for MRI, CSF, and cognitive assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• icosapent ethyl (IPE)

How Is the Trial Designed?

Group I: icosapent ethyl (IPE) Experimental Treatment 1 Intervention

Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo

Group II: placebo Placebo Group 1 Intervention

Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.032413

Cost‐Effectiveness of Icosapent Ethyl in REDUCE‐IT USA At $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost‐effective at $11.48 per day for conventional ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10124620/

Cost-Effectiveness of Icosapent Ethyl (IPE) for the ... IPE represents an important new treatment for the reduction of ischemic CV events in statin-treated patients with elevated triglycerides.

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.038656

Cardiovascular Outcomes With Icosapent Ethyl by Baseline ... Icosapent ethyl is effective in reducing cardiovascular events among indicated patients irrespective of baseline low‐density lipoprotein ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10184960/

A Critical Review of Icosapent Ethyl in Cardiovascular Risk ... The efficacy of using highly purified IPE for CV risk reduction has been reviewed in various studies including REDUCE-IT, JELIS, and ANCHOR and ...

5. frontiersin.org frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1220017/full

Global eligibility and cost effectiveness of icosapent ethyl in ... Icosapent ethyl (IPE) is a purified eicosapentaenoic acid–only omega-3 fatty acid that significantly reduced cardiovascular (CV) events in patients receiving ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/202057s035lbl.pdf

Vascepa (icosapent ethyl) - accessdata.fda.gov No overall differences in safety or effectiveness were observed. Page 5 of 14. Reference ID: 4533779. This label may not be the latest approved by FDA. For ...

7. camberpharma.com camberpharma.com/wp-content/uploads/2024/03/Icosapent-ethyl-Capsules-SDS.pdf

Icosapent-ethyl-Capsules-SDS.pdf Eye/Face Protection: Wear safety glasses with side shields wherever the potential exists for direct exposure to capsules. Skin Protection: Use disposable ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1933287425000066

Comparison of product label vs real-world safety data from ... The REDUCE-IT trial demonstrated significant reductions in cardiovascular events with icosapent ethyl (IPE) treatment among patients with elevated ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37873598/

Real-world safety of icosapent ethyl: analysis based on ... This study provides a comprehensive real-world safety profile of IPE, which indicates that IPE is well-tolerated.