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

Overview

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 Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: June 30, 2024

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.

Interventions

  • Dietary Supplement: EPA+DHA
    • EPA+DHA are the n-3 polyunsaturated fatty acids contained in fish oil
  • Other: placebo
    • placebo contains mineral oil

Arms, Groups and Cohorts

  • 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)
  • 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)

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 55 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ohio State University
  • Collaborator
    • National Institute on Aging (NIA)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jodi C McDaniel, PhD, Principal Investigator, Ohio State University, College of Nursing
  • Overall Contact(s)
    • Jodi C. McDaniel, PhD, 614-292-1345, mcdaniel.561@osu.edu

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