Chronic Venous Leg UlcersNCT03576989
Impact of Omega-3 Fatty Acid Oral Therapy on Healing of Chronic Venous Leg Ulcers in Older Adults
A study testing EPA+DHA in people with Chronic Venous Leg Ulcers, run by Ohio State University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Chronic Venous Leg Ulcers
- What is being tested?
- EPA+DHA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2019to 18 Dec 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Ohio State University College of Nursing
Columbus, Ohio, 43210
About this study
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.
Read the 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.
- Conditions
- Chronic Venous Leg Ulcers
- Being tested
- EPA+DHA, placebo
- Keywords
- leg ulcer, fish oil, wounds
- Medical subject headings
- Leg Ulcer, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EPA+DHADietary supplement
Also called eicosapentaenoic acid + docosahexaenoic acid, fish oil
EPA+DHA are the n-3 polyunsaturated fatty acids contained in fish oil
placeboOther
Also called mineral oil
placebo contains mineral oil
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 0, 4, 8 and 12 weeks
Secondary outcomes (2)
Venous Insufficiency Epidemiological and Economic Study Quality Of Life/Symptom (VEINES-QOL/Sym) Questionnaire
The VEINES-QOL/Sym questionnaire consists of 26 items designed to assess both disease-specific quality of life (VEINES-QOL) and symptom severity (VEINES-Sym) in individuals with venous disorders. The instrument evaluates two separate metrics, both of which are calculated using the mean of standardized z-scores. The typical theoretical range for both is roughly 0 to 100, with a mean population standard of 50. The final score was calculated after calculating the mean of all z scores, which were multiplied by 10, and then added to 50. Higher scores indicate better quality of life and fewer symptoms (i.e., a more favorable outcome). VEINES-QOL/Sym scores are expressed as Z-scores standardized to a reference population, with a mean of 0 and standard deviation of 1. A Z-score of 0 represents the population mean. Higher Z-scores indicate better quality of life and fewer venous insufficiency symptoms, while lower Z-scores indicate worse outcomes.
Measured: 0, 12 weeks
Venous Clinical Severity Score (VCSS)
The Venous Clinical Severity Score (VCSS) is a 10-item, 30-point scoring system used to assess and track the severity of chronic venous disease (CVD) and its response to treatment, ranging from 0 (none) to 3 (severe) for parameters like pain, ulcers, and edema. Scores can range from 0 to 30 with higher scores meaning more severe venous disease. The average scores at Weeks 0, 4, 8 and 12 were calculated for each treatment group.
Measured: 0, 4, 8, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2018
- Study start15 Apr 2019
- Primary completion18 Dec 2024
- Study completion18 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Venous Leg UlcersStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2-group randomized, double-blind, repeated measures design
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Jodi C McDaniel, PhD, Principal investigator, Ohio State University, College of Nursing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03576989
- Sponsor's protocol ID
- 2018H0261
- Other IDs
- R01AG059981
- Status last verified
- Jun 2026
- First submitted
- 13 Jun 2018
- Last updated
- 17 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31948466
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Omega-3 Fatty Acid Oral Therapy on Healing of Chronic Venous Leg Ulcers in Older Adults
- ClinicalTrials.gov ID
- NCT03576989
- Acronym / sponsor ID
- 2018H0261
- Conditions
- Chronic Venous Leg Ulcers
- Keywords
- leg ulcer, fish oil, wounds
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 18 Dec 2024 (actual)
- Study completion
- 18 Dec 2024 (actual)
- First posted
- 5 Jul 2018 (actual)
- Results
- Posted 17 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 2-group randomized, double-blind, repeated measures design
| Arm | Type | Receives |
|---|---|---|
| EPA+DHA Group | Experimental | Dietary Supplement: EPA+DHA12 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 Group | Placebo comparator | Other: placebo12 weeks of daily oral therapy with placebo (three opaque softgels to provide a total daily intake of 2.5 mL of mineral oil) |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EPA+DHAAlso: eicosapentaenoic acid + docosahexaenoic acid, fish oilEPA+DHA are the n-3 polyunsaturated fatty acids contained in fish oil | Dietary supplement | EPA+DHA Group |
| placeboAlso: mineral oilplacebo contains mineral oil | Other | Placebo Group |
Primary outcome
Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE5
Time frame: 0, 4, 8 and 12 weeks
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.
Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE11
Time frame: 0, 4, 8 and 12 weeks
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.
Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE12
Time frame: 0, 4, 8 and 12 weeks
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.
Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE15
Time frame: 0, 4, 8 and 12 weeks
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.
Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE18
Time frame: 0, 4, 8 and 12 weeks
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.
Comparison of Intervention and Control Groups in IL-1β Levels (Log pg/mL)
Time frame: 0, 4, 8 and 12 weeks
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.
Comparison of Intervention and Control Groups in IL-6 Levels (Log pg/mL)
Time frame: 0, 4, 8 and 12 weeks
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.
1. Comparison of Intervention and Control Groups in TNF-α Levels (Log pg/mL)
Time frame: 0, 4, 8 and 12 weeks
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.
Comparison of Intervention and Control Groups in IFN-γ Levels (Log pg/mL)
Time frame: 0, 4, 8 and 12 weeks
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.
Intervention Effects on Polymorphonuclear Leukocyte (PMN) Activation (Log Cells/µL)
Time frame: 0, 4, 8 and 12 weeks
Reported values reflect PMN activation in plasma, expressed as log-transformed concentrations (cells/µL) at Weeks 4, 8, and 12.
Intervention Effects on Polymorphonuclear Leukocyte (PMN) - Derived Matrix Metalloproteinase-8 (MMP-8) Levels (Log pg/mg) in Wound Fluid
Time frame: 0, 4, 8 and 12 weeks
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.
Intervention Effects on Polymorphonuclear Leukocyte (PMN) - Derived Human Neutrophil Elastase (HNE, ELA2) Levels (Log pg/mg) in Wound Fluid
Time frame: 0, 4, 8 and 12 weeks
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.
Comparison of Intervention vs. Control Groups in the Percent Change in Wound Area Relative to Baseline
Time frame: 0, 4, 8 and 12 weeks
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).
2 secondary outcomes
Venous Insufficiency Epidemiological and Economic Study Quality Of Life/Symptom (VEINES-QOL/Sym) Questionnaire
Time frame: 0, 12 weeks
Venous Clinical Severity Score (VCSS)
Time frame: 0, 4, 8, 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31948466McDaniel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jodi C McDaniel, PhD principal investigator
Ohio State University, College of Nursing
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EPA+DHA in people with Chronic Venous Leg Ulcers, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intervention Effects on Plasma Levels of Lipid Mediator of Inflammation HEPE5 (time frame: 0, 4, 8 and 12 weeks). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03576989, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.