Clinical trial NCT03576989: Impact of Omega-3 Fatty Acid Oral Therapy on Healing of Chronic Venous Leg Ulcers in Older Adults
Official title: Impact of Omega-3 Fatty Acid Oral Therapy on Healing of Chronic Venous Leg Ulcers in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Venous Leg Ulcers
Keywords: leg ulcer, fish oil, wounds
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-07-05
Enrollment: 296
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2-group randomized, double-blind, repeated measures design
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in EPA+DHA-derived lipid mediators
timeFrame: 0, 4, 8 and 12 weeks
measure: Change in inflammatory cytokines
timeFrame: 0, 4, 8 and 12 weeks
measure: Change in polymorphonuclear leukocyte (PMN) activation
timeFrame: 0, 4, 8 and 12 weeks
measure: Change in PMN-derived proteases
timeFrame: 0, 4, 8 and 12 weeks
measure: Change in reduction in wound area
timeFrame: 0, 4, 8 and 12 weeks
Secondary outcomes:
measure: inflammatory cytokine gene expression
timeFrame: 0, 4, 8 and 12 weeks
measure: recurrence of chronic venous leg ulcers
timeFrame: 3 months beyond Week 12 time point in participants whose leg ulcers have healed by Week 12
measure: Change in symptom of pain
timeFrame: 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)
measure: quality of life using the VEINES-QOL/Sym questionnaire
timeFrame: 0, 12 weeks ((and at 3 month timepoint beyond Week 12 in participants in extended study - with healed leg ulcers by Week 12)
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University College of Nursing
state: Ohio
Study officials:
affiliation: Ohio State University, College of Nursing
name: Jodi C McDaniel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.