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

NCT03576989 | Completed Results DMC

• 2 other identifiers: 2018H0261R01AG059981
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Venous Leg Ulcers

Keywords

leg ulcer, fish oil, wounds

Outcome Measures

Primary Outcomes (13)

• Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE5

  Intervention effects on plasma levels of lipid mediator of inflammation HEPE5 measured in pg/mL at Weeks 4, 8 and 12. 5-HEPE (5-hydroxy-eicosapentaenoic acid) is an eicosanoid derived from eicosapentaenoic acid (EPA) via the 5-lipoxygenase pathway. It functions as an anti-inflammatory lipid mediator, in part through the generation of reactive oxygen species. Plasma levels of 5-HEPE (also known as HEPE5) were measured using liquid chromatography-mass spectrometry.

  0, 4, 8 and 12 weeks

• Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE11

  Intervention effects on plasma levels of lipid mediator of inflammation HEPE11 measured in pg/mL at Weeks 4, 8 and 12. 11-HEPE (11-hydroxy-5Z,8Z,12E,14Z,17Z-eicosapentaenoic acid) is a monohydroxy fatty acid derived from eicosapentaenoic acid (EPA). In research, it is commonly studied as a lipid mediator (eicosanoid) associated with anti-inflammatory processes. Plasma levels of 11-HEPE (also known as HEPE11) were quantified using liquid chromatography-mass spectrometry.

  0, 4, 8 and 12 weeks

• Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE12

  Intervention effects on plasma levels of lipid mediator of inflammation HEPE12 at Weeks 4, 8 and 12. 12-HEPE (12-hydroxyeicosapentaenoic acid) is an omega-3 fatty acid metabolite formed from eicosapentaenoic acid (EPA) via the 12-lipoxygenase pathway. It functions as a signaling lipid that helps mediate the beneficial effects of EPA and exhibits potent anti-inflammatory properties. Plasma levels of 12-HEPE (HEPE12) were quantified using liquid chromatography-mass spectrometry.

  0, 4, 8 and 12 weeks

• Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE15

  Intervention effects on plasma levels of lipid mediator of inflammation HEPE15 measured in pg/mL at Weeks 4, 8 and 12. 15-HEPE (15-hydroxyeicosapentaenoic acid) is an anti-inflammatory metabolite produced from the omega-3 fatty acid eicosapentaenoic acid (EPA) via the 15-lipoxygenase pathway. It functions as a pro-resolving lipid mediator, contributing to the resolution of inflammation. Plasma levels of 15-HEPE (HEPE15) were quantified using liquid chromatography-mass spectrometry.

  0, 4, 8 and 12 weeks

• Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE18

  Intervention effects on plasma levels of lipid mediator of inflammation HEPE18 measured in pg/mL at Weeks 4, 8 and 12. 18-HEPE (18-hydroxyeicosapentaenoic acid) is an anti-inflammatory metabolite of the omega-3 fatty acid eicosapentaenoic acid (EPA) and serves as a precursor for E-series resolvins. E-series resolvins actively terminate inflammatory responses, promote the resolution of inflammation, and support tissue repair. They exert potent anti-inflammatory effects by limiting neutrophil infiltration and suppressing pro-inflammatory cytokine production. Plasma levels of 18-HEPE (HEPE18) were quantified using liquid chromatography-mass spectrometry.

  0, 4, 8 and 12 weeks

• Comparison of Intervention and Control Groups in IL-1β Levels (Log pg/mL)

  Plasma levels of IL-1β were quantified using a commercially available V-PLEX Human Biomarker Plex Kit (Meso Scale Diagnostics). Reported values reflect the group plasma IL-1β levels expressed as log-transformed concentrations (pg/mL). The IL-1β data are presented on a logarithmic (log) scale to normalize the distribution of cytokine concentrations, which are typically right-skewed. Because log-transformed values are used, negative means can occur when the original (raw) cytokine concentrations are less than 1 (in the units of measurement, pg/mL). Thus, the negative values at baseline do not indicate 'negative' cytokine levels, but rather low concentrations on the original scale. Across time points, less negative (i.e., higher) log values indicate higher cytokine concentrations, whereas more negative values indicate lower concentrations. Therefore, changes in the mean log values over time reflect relative increases or decreases in IL-1β levels.

  0, 4, 8 and 12 weeks

• Comparison of Intervention and Control Groups in IL-6 Levels (Log pg/mL)

  Plasma levels of IL-6 were quantified using a commercially available V-PLEX Human Biomarker Plex Kit (Meso Scale Diagnostics). Reported values reflect the group plasma IL-6 levels expressed as log-transformed concentrations (pg/mL). The data are presented on a logarithmic (log) scale to normalize the distribution of cytokine concentrations, which are typically right-skewed. Because log-transformed values are used, negative means can occur when the original (raw) cytokine concentrations are less than 1 (in the units of measurement, pg/mL). Thus, the negative values at baseline do not indicate 'negative' cytokine levels, but rather low concentrations on the original scale. Across time points, less negative (i.e., higher) log values indicate higher cytokine concentrations, whereas more negative values indicate lower concentrations. Therefore, changes in the mean log values over time reflect relative increases or decreases in IL-6 levels.

  0, 4, 8 and 12 weeks

• 1. Comparison of Intervention and Control Groups in TNF-α Levels (Log pg/mL)

  Plasma levels of TNF-α were quantified using a commercially available V-PLEX Human Biomarker Plex Kit (Meso Scale Diagnostics). Reported values reflect the group plasma TNF-α levels expressed as log-transformed concentrations (pg/mL). The data are presented on a logarithmic (log) scale to normalize the distribution of cytokine concentrations, which are typically right-skewed. Because log-transformed values are used, negative means can occur when the original (raw) cytokine concentrations are less than 1 (in the units of measurement, pg/mL). Thus, the negative values at baseline do not indicate 'negative' cytokine levels, but rather low concentrations on the original scale. Across time points, less negative (i.e., higher) log values indicate higher cytokine concentrations, whereas more negative values indicate lower concentrations. Therefore, changes in the mean log values over time reflect relative increases or decreases in TNF-α levels.

  0, 4, 8 and 12 weeks

• Comparison of Intervention and Control Groups in IFN-γ Levels (Log pg/mL)

  Plasma levels of IFN-γ were quantified using a commercially available V-PLEX Human Biomarker Plex Kit (Meso Scale Diagnostics). Reported values reflect the group plasma IFN-γ levels expressed as log-transformed concentrations (pg/mL). The data are presented on a logarithmic (log) scale to normalize the distribution of cytokine concentrations, which are typically right-skewed. Because log-transformed values are used, negative means can occur when the original (raw) cytokine concentrations are less than 1 (in the units of measurement, pg/mL). Thus, the negative values at baseline do not indicate 'negative' cytokine levels, but rather low concentrations on the original scale. Across time points, less negative (i.e., higher) log values indicate higher cytokine concentrations, whereas more negative values indicate lower concentrations. Therefore, changes in the mean log values over time reflect relative increases or decreases in IFN-γ levels.

  0, 4, 8 and 12 weeks

• Intervention Effects on Polymorphonuclear Leukocyte (PMN) Activation (Log Cells/µL)

  Reported values reflect PMN activation in plasma, expressed as log-transformed concentrations (cells/µL) at Weeks 4, 8, and 12.

  0, 4, 8 and 12 weeks

• Intervention Effects on Polymorphonuclear Leukocyte (PMN) - Derived Matrix Metalloproteinase-8 (MMP-8) Levels (Log pg/mg) in Wound Fluid

  MMP-8, also known as neutrophil collagenase, is an enzyme that degrades collagen types I, II, and III and contributes to tissue remodeling and inflammatory processes. Wound fluid levels of MMP-8 were quantified using the MMP-8, neutrophil collagenase, Biotrak enzyme-linked immunosorbent assay kit (GE Healthcare Bio-Sciences Corp., Piscataway,NJ). Reported values reflect wound fluid MMP-8 levels, expressed as log-transformed concentrations (pg/mg) at Weeks 0, 4, 8, and 12.

  0, 4, 8 and 12 weeks

• Intervention Effects on Polymorphonuclear Leukocyte (PMN) - Derived Human Neutrophil Elastase (HNE, ELA2) Levels (Log pg/mg) in Wound Fluid

  HNE is a potent serine protease stored in neutrophil granules that plays a key role in degrading bacteria and host tissue during inflammatory responses. Wound fluid levels of HNE were quantified using the InnuozymeTM Human Neutrophil Elastase Immunocapture Activity Assay Kit (Calbiochem, EMD Biosciences Inc., San Diego, CA). Reported values reflect wound fluid HNE levels, expressed as log-transformed concentrations (pg/mg) at Weeks 0, 4, 8 and 12.

  0, 4, 8 and 12 weeks

• Comparison of Intervention vs. Control Groups in the Percent Change in Wound Area Relative to Baseline

  Percentage Area Reduction (PAR) is a valuable, widely used metric for evaluating and comparing the effectiveness of wound healing interventions in research. PAR was calculated at each follow-up time point (Weeks 4, 8, and 12) relative to the baseline. It represents the percentage change in wound size (area in cm2) from baseline, computed as: "PAR"=("Baseline Area" -"Follow-up Area" )/"Baseline Area" ×100 Positive PAR values indicate a reduction in wound area (i.e., healing), whereas negative values indicate an increase in wound size compared to baseline (i.e., the wound has enlarged).

  0, 4, 8 and 12 weeks

Secondary Outcomes (2)

• Venous Insufficiency Epidemiological and Economic Study Quality Of Life/Symptom (VEINES-QOL/Sym) Questionnaire

  0, 12 weeks

• Venous Clinical Severity Score (VCSS)

  0, 4, 8, 12 weeks

Study Arms (2)

EPA+DHA Group

EXPERIMENTAL

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

Placebo Group

PLACEBO COMPARATOR

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

Interventions

EPA+DHA DIETARY_SUPPLEMENT

EPA+DHA are the n-3 polyunsaturated fatty acids contained in fish oil

Also known as: eicosapentaenoic acid + docosahexaenoic acid, fish oil

EPA+DHA Group

placebo OTHER

placebo contains mineral oil

Also known as: mineral oil

Placebo Group

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

The Ohio State University College of Nursing

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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.

  PMID: 31948466 DERIVED

MeSH Terms

Conditions

Leg Ulcer; Wounds and Injuries

Interventions

Eicosapentaenoic Acid; Docosahexaenoic Acids; Fish Oils; Mineral Oil

Condition Hierarchy (Ancestors)

Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Oils; Petrolatum; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Jodi McDaniel
• Organization: Ohio State University College of Nursing

mcdaniel.561@osu.edu

614-247-8366

Study Officials

• Jodi C McDaniel, PhD

  Ohio State University, College of Nursing

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Investigators, participants and care providers blinded as to treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2-group randomized, double-blind, repeated measures design

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: July 5, 2018
• Study Start: April 15, 2019
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: June 17, 2026
• Results First Posted: June 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)