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

Chronic Venous Leg Ulcers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03576989
• Other study ID #: 2018H0261
• Secondary ID: R01AG059981
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2019
• Est. completion date: October 31, 2024

Study information

• Verified date: April 2024
• Source: Ohio State University
• Contact: Jodi C. McDaniel, PhD
• Phone: 614-292-1345
• Email: mcdaniel.561[@]osu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: October 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Venous Leg Ulcers
• Leg Ulcer
• Ulcer
• Varicose Ulcer

Intervention

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

Other:
• placebo
placebo contains mineral oil

Locations

Country	Name	City	State
United States	The Ohio State University College of Nursing	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Ohio State University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Change in inflammatory cytokines	plasma and wound fluid levels of pro- and anti-inflammatory cytokines	0, 4, 8 and 12 weeks
Primary	Change in polymorphonuclear leukocyte (PMN) activation	blood and wound fluid levels of PMN activation	0, 4, 8 and 12 weeks
Primary	Change in PMN-derived proteases	wound fluid levels of PMN-derived proteases	0, 4, 8 and 12 weeks
Primary	Change in reduction in wound area	reduction in wound area measured in cm2	0, 4, 8 and 12 weeks
Secondary	inflammatory cytokine gene expression	inflammatory cytokine gene expression by neutrophils and monocytes from blood	0, 4, 8 and 12 weeks
Secondary	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
Secondary	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)
Secondary	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)