Impact of Omega-3 Fatty Acid Oral Therapy on Healing of Chronic Venous Leg Ulcers in Older Adults

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 chronic venous leg ulcers (CVLUs) by reducing the chronic inflammation at wound sites that prevents healing progression. If this systemic, nutrient intervention is found to alter the microenvironment of CVLUs, the science of wound healing and care of patients with CVLUs will be vastly improved.

Study Overview

• Status: Completed
• Conditions: Chronic Venous Leg Ulcers
• Intervention / Treatment: Dietary supplement: EPA+DHA; Other: placebo

Detailed Description

The pathogenesis of CVLU involves high numbers of activated polymorphonuclear leukocytes (PMN) that are associated with persistent inflammation in the wound bed. The proposed research is to test the efficacy of an oral, nutrient intervention containing the bioactive components of fish oil (eicosapentaenoic acid - EPA + docosahexaenoic acid - DHA) to assuage PMN activity and promote healing. The study plans to include 248 successive eligible adults ≥ 55 years of age with CVLUs who continue to receive standard care at two university out-patient wound clinics. Participants will be randomized to 2 groups: 12 weeks of daily oral therapy with EPA+DHA (1.87 g/d of EPA + 1.0 g/d of DHA) or daily oral therapy with placebo. At 0, 4, 8 and 12 weeks, across the 2 groups, three specific aims will be pursued:

Aim 1. Compare levels of EPA+DHA-derived lipid mediators, and inflammatory cytokines in blood and CVLU fluid.

Subaim 1a. Compare inflammatory cytokine gene expression by PMNs in blood (neutrophils and monocytes).

Aim 2. Compare PMN activation (blood, CVLU fluid), and PMN-derived protease levels (CVLU fluid).

Aim 3. Compare reduction in wound area, controlling for key factors known to affect healing, and determine relationships with lipid mediators, cytokines and PMN activation.

Subaim 3a. Compare frequency of CVLU recurrence and levels of study variables in blood between 2 subgroups within the EPA+DHA group with healed CVLUs (after 3 additional months of EPA+DHA therapy versus placebo therapy beyond Week 12 time point).

Subaim 3b. Compare the symptom of pain at all time points and quality of life at first and last study visits across the 2 groups and 2 subgroups.

• Study Type: Interventional
• Enrollment (Actual): 296
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University College of Nursing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Women and men ≥ 55 years of age with:

• A CVLU between the ankle and knee that has been present for at least 4 weeks, but not longer than 12 months, prescribed compression therapy with 1-4 layer bandaging;
• Ankle brachial pressure index (ABPI) between 0.7 and 1.2;
• Target wound area of 2-60 cm2 who can
• Read and understand English or Spanish, and
• Provide consent.

Exclusion Criteria:

• Fish allergy;
• Corticosteroids or selective cyclooxygenase (COX)-2 inhibitors (e.g., Celebrex); non- steroidal anti-inflammatory drugs (NSAIDS) > 2x/week (exception: aspirin 81 mg/day);
• Autoimmune diseases;
• Chemotherapy within 6 months of Week 0;
• Diabetes if HbA1c > 12% or ulcer complicated by cellulitis, exposed tendon or bone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EPA+DHA Group; 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)	Dietary supplement: EPA+DHA; EPA+DHA are the n-3 polyunsaturated fatty acids contained in fish oil; Other Names: fish oil; eicosapentaenoic acid + docosahexaenoic acid
Placebo Comparator: Placebo Group; 12 weeks of daily oral therapy with placebo (three opaque softgels to provide a total daily intake of 2.5 mL of mineral oil)	Other: placebo; placebo contains mineral oil; Other Names: mineral oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in EPA+DHA-derived lipid mediators	plasma and wound fluid levels of EPA+DHA-derived lipid mediators of inflammation	0, 4, 8 and 12 weeks
Change in inflammatory cytokines	plasma and wound fluid levels of pro- and anti-inflammatory cytokines	0, 4, 8 and 12 weeks
Change in polymorphonuclear leukocyte (PMN) activation	blood and wound fluid levels of PMN activation	0, 4, 8 and 12 weeks
Change in PMN-derived proteases	wound fluid levels of PMN-derived proteases	0, 4, 8 and 12 weeks
Change in reduction in wound area	reduction in wound area measured in cm2	0, 4, 8 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammatory cytokine gene expression	inflammatory cytokine gene expression by neutrophils and monocytes from blood	0, 4, 8 and 12 weeks
recurrence of chronic venous leg ulcers	frequency of recurrence of chronic venous leg ulcers after healing	3 months beyond Week 12 time point in participants whose leg ulcers have healed by Week 12
Change in symptom of pain	pain related to venous leg ulcer measured using the Venous Clinical Severity Score (VCSS)	0, 4, 8 and 12 weeks (and at 3 month timepoint beyond Week 12 in participants in extended study - with healed leg ulcers by Week 12)
quality of life using the VEINES-QOL/Sym questionnaire	quality of life related to venous leg ulcer measured using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms questionnaire	0, 12 weeks ((and at 3 month timepoint beyond Week 12 in participants in extended study - with healed leg ulcers by Week 12)

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Jodi C McDaniel, PhD, Ohio State University, College of Nursing

Publications and helpful links

General Publications

• McDaniel JC, Rausch J, Tan A. 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. Trials. 2020 Jan 16;21(1):93. doi: 10.1186/s13063-019-3970-7.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): December 18, 2024
• Study Completion (Actual): December 18, 2024

Study Registration Dates

• First Submitted: June 13, 2018
• First Submitted That Met QC Criteria: June 22, 2018
• First Posted (Actual): July 5, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: leg ulcer, fish oil, wounds
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Varicose Ulcer; Leg Ulcer; Dermatologic Agents; Emollients; Mineral Oil
• Other Study ID Numbers: 2018H0261; R01AG059981 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No