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

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 ≥
60 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 (2.5 g/d of EPA + 0.5 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.

Inclusion Criteria:

Women and men ≥ 60 years of age with:

- A CVLU between the ankle and knee that has been present for at least 6 weeks, but not
longer than 6 months, prescribed compression therapy with 2-4 component bandaging;

- Ankle brachial pressure index (ABPI) between 0.7 and 1.2;

- Target wound area of 2-20 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 6) ulcer complicated by cellulitis, exposed tendon or
bone.