Omega-3 Supplements for Leg Ulcers

Overseen By Sandra Solove, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University

Must not be taking: Corticosteroids, COX-2 inhibitors, NSAIDs

Disqualifiers: Fish allergy, Autoimmune diseases, Diabetes, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether omega-3 supplements can help heal chronic venous leg ulcers (CVLUs) by reducing inflammation. Participants will take either omega-3 supplements (specifically EPA+DHA) or a placebo (a pill with no active ingredients) for 12 weeks. The goal is to determine if these supplements can improve wound healing for individuals with long-standing leg ulcers. This trial suits those aged 55 and older with a CVLU present for at least 4 weeks but less than a year, who are also using compression therapy. As an unphased trial, it offers a unique opportunity to contribute to research that could lead to new treatment options for CVLUs.

Do I need to stop taking my current medications for the trial?

You may need to stop certain medications. The trial excludes people taking corticosteroids, COX-2 inhibitors, and NSAIDs more than twice a week, except for aspirin 81 mg/day.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids, COX-2 inhibitors, and NSAIDs more than twice a week, except for aspirin at 81 mg per day.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that omega-3 fatty acids, such as EPA and DHA found in fish oil, are generally safe for people. Studies have found that most individuals can take these supplements without major side effects, though some might experience mild issues like a fishy aftertaste, nausea, or stomach discomfort.

Earlier research on EPA and DHA did not identify any serious problems. These studies examined how these nutrients affect healing and inflammation. For those considering participation in a trial with omega-3 supplements, the evidence suggests it is likely safe. However, consulting a doctor is essential to ensure it is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike traditional treatments for leg ulcers, which often involve topical creams, compression therapy, or surgical interventions, the investigational treatment using EPA and DHA is derived from omega-3 fatty acids and taken orally. Researchers are excited because these omega-3s have anti-inflammatory properties that could promote healing from within, offering a potentially less invasive and more systemic approach to treatment. Additionally, the use of omega-3s might reduce the risk of side effects associated with more aggressive standard treatments, providing a promising alternative for patients struggling with chronic leg ulcers.

What evidence suggests that this treatment might be an effective treatment for leg ulcers?

This trial will compare the effects of omega-3 fatty acids, specifically EPA and DHA found in fish oil, with a placebo for healing chronic venous leg ulcers (CVLUs). Studies have shown that EPA and DHA can help heal CVLUs by potentially reducing swelling around wounds, often aiding in faster healing. Some findings suggest that combining EPA and DHA with regular wound care could improve healing. Evidence also shows that omega-3s may alter the wound's environment, making it more suitable for healing. While these results are promising, further research is needed to confirm their effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

Jodi C McDaniel, PhD, RN

Principal Investigator

Ohio State University, College of Nursing

Are You a Good Fit for This Trial?

This trial is for men and women aged 55 or older with chronic venous leg ulcers between the ankle and knee, present for 4 weeks to 12 months. Participants must have a wound area of 2-60 cm2, understand English or Spanish, have certain blood flow levels in their legs (ABPI of 0.7-1.2), be on prescribed compression therapy, and able to consent. Excluded are those taking certain anti-inflammatory drugs more than twice a week (except low-dose aspirin), with fish allergies, autoimmune diseases, poorly controlled diabetes or recent chemotherapy.

Inclusion Criteria

Ability to provide consent

I am 55 or older with a leg ulcer between my ankle and knee, present for 1-12 months, and prescribed compression therapy.

My wound is between 2 and 60 square centimeters in size.

Exclusion Criteria

You are allergic to fish.

My diabetes is severe with HbA1c over 12% or I have a serious foot ulcer.

I have not had chemotherapy in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 12 weeks of daily oral therapy with either EPA+DHA or placebo

12 weeks

Visits at 0, 4, 8, and 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including recurrence of ulcers and quality of life

3 months

1 visit (in-person) at 3 months post-treatment

Open-label extension (optional)

Participants with healed leg ulcers by Week 12 may continue with EPA+DHA therapy for an additional 3 months

3 months

What Are the Treatments Tested in This Trial?

Interventions

• EPA+DHA
• placebo

Trial Overview The study tests if oral Omega-3 fatty acids (EPA+DHA from fish oil) can help heal chronic leg ulcers by reducing inflammation at the wound site compared to a placebo. The goal is to see if this nutrient intervention changes the healing environment of these wounds.

How Is the Trial Designed?

Group I: EPA+DHA Group Experimental Treatment 1 Intervention

12 weeks of daily oral therapy with EPA+DHA (three opaque softgels to provide a total daily intake of 1.87 g of EPA + 1.0 g of DHA)

Group II: Placebo Group Placebo Group 1 Intervention

12 weeks of daily oral therapy with placebo (three opaque softgels to provide a total daily intake of 2.5 mL of mineral oil)

EPA+DHA is already approved in United States, European Union for the following indications:

Approved in United States as Fish Oil for:

• Dietary Supplement

Approved in European Union as Fish Oil for:

• Dietary Supplement

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

This trial is testing an oral therapy with fish oil components (EPA and DHA) on 248 adults aged 55 and older with chronic venous leg ulcers (CVLUs) to see if it can reduce inflammation and promote healing over 12 weeks.

If successful, this therapy could provide a new treatment option for CVLUs by targeting excessive activation of immune cells that keep these wounds in a chronic state, potentially improving healing outcomes and quality of life for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of omega-3 fatty acid oral therapy on healing of chronic venous leg ulcers in older adults: Study protocol for a randomized controlled single-center trial. McDaniel, JC., Rausch, J., Tan, A.[2020]

Acellular fish skin grafts from Atlantic cod, rich in omega-3 fatty acids like EPA and DHA, have shown increased efficacy in treating chronic, non-healing wounds such as diabetic foot ulcers, leading to faster healing rates compared to standard treatments.

The unique lipid profile of fish skin grafts not only promotes wound closure but also provides barrier protection against bacteria and modulates the inflammatory response, enhancing overall wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fish Skin Grafts with Omega-3 for Treatment of Chronic Wounds: Exploring the Role of Omega-3 Fatty Acids in Wound Healing and A Review of Clinical Healing Outcomes. Seth, N., Chopra, D., Lev-Tov, H.[2022]

In a study involving 40 critically ill patients with pressure ulcers, those who received a fish oil- and micronutrient-enriched formula showed significant improvements in immune function, indicated by increased levels of specific adhesion molecules on immune cells.

Patients on the study formula did not experience worsening of their pressure ulcers over time, while the control group did, suggesting that the enriched formula may help prevent the deterioration of pressure ulcers through its effects on immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteral n-3 fatty acids and micronutrients enhance percentage of positive neutrophil and lymphocyte adhesion molecules: a potential mediator of pressure ulcer healing in critically ill patients. Theilla, M., Schwartz, B., Zimra, Y., et al.[2012]

Omega-3-acid ethyl esters were found to be highly effective in treating refractory pressure ulcers and stasis dermatitis, as demonstrated in two case studies involving a 21-year-old female and a 76-year-old male, with complete healing observed in 10 and 12 weeks respectively.

This report suggests that oral administration of omega-3-acid ethyl esters could be a promising alternative treatment for patients who do not respond to traditional topical therapies for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapy using omega-3-Acid ethyl esters for decubitus ulcers and stasis dermatitis: a case report. Nagai, K., Matsumaru, K., Hirai, I., et al.[2020]

Oral therapy with EPA and DHA significantly reduced activated polymorphonuclear leukocytes (PMNs) in chronic venous leg ulcers (CVLUs), indicating a potential mechanism for enhancing healing by modulating inflammation.

Patients receiving EPA and DHA showed greater reductions in wound area (76% by Day 56) compared to the placebo group (59%), suggesting that these bioactive components can improve healing outcomes when added to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EPA + DHA supplementation reduces PMN activation in microenvironment of chronic venous leg ulcers: A randomized, double-blind, controlled study. McDaniel, JC., Szalacha, L., Sales, M., et al.[2022]

In a 12-week study involving 60 subjects with diabetic foot ulcers, supplementation with 1000mg of omega-3 fatty acids from flaxseed oil significantly reduced ulcer size compared to a placebo, indicating improved wound healing.

The omega-3 supplementation also led to notable improvements in metabolic markers, including decreased insulin levels and insulin resistance, as well as increased antioxidant capacity, suggesting that it may enhance healing indirectly through better metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and metabolic response to flaxseed oil omega-3 fatty acids supplementation in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Soleimani, Z., Hashemdokht, F., Bahmani, F., et al.[2022]

Older adults with chronic venous leg ulcers (CVLUs) consumed significantly lower levels of vitamin C and higher levels of sodium, sugar, and saturated fat compared to recommended dietary allowances, which may negatively impact their wound healing.

The study suggests that a multidisciplinary approach, including regular dietary assessments and personalized dietary interventions, could enhance wound healing and overall health in this population of older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional profile of older adults with chronic venous leg ulcers: a pilot study. McDaniel, JC., Kemmner, KG., Rusnak, S.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6966808/

Impact of omega-3 fatty acid oral therapy on healing ... The primary outcome measure with respect to the effectiveness of EPA + DHA oral therapy in the treatment of CVLUs is time to complete wound healing. We define ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31948466/

Impact of omega-3 fatty acid oral therapy on healing of chronic ... This trial will provide new evidence about the effectiveness of EPA + DHA oral therapy to target and reduce excessive PMN activation systemically and locally ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03576989

Impact of Omega-3 Fatty Acid Oral Therapy on Healing ... The purpose of this study is to test the efficacy of an oral, nutrient intervention containing the bioactive components of fish oil to promote healing of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01754506

Testing Fish Oil Derivatives In Healing Of Chronic Venous ... The purpose of this study is to test the efficacy of an oral, nutrient intervention containing the bioactive components of fish oil to promote healing of ...

5. mdpi.com mdpi.com/2304-8158/10/10/2306

New Insights on the Effects of Dietary Omega-3 Fatty Acids ... As a conclusion, the authors predict that treatment with EPA plus DHA in combination with conventional topical therapy could substantially improve the healing ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9288800/

EPA+DHA supplementation reduces PMN activation in ... This randomized controlled study compared the effectiveness of oral EPA + DHA therapy to a placebo for reducing PMN activation in CVLU microenvironments.