Effects of EPA Supplementation on Patients With Unresectable Hepatocellular Carcinoma.

June 17, 2026 updated by: Ángel Lanas Arbeloa, Instituto de Investigación Sanitaria Aragón

Effects of Nutritional Supplementation With Eicosapentaenoic Acid (EPA) on Body Composition and Systemic Pro-inflammatory and Pro-resolving Mediators in Patients Diagnosed With Unresectable Hepatocellular Carcinoma.

Dietary intervention with eicosapentaenoic acid combined with chemotherapy may shift inflammatory mediators toward resolution in non-resectable hepatocarcinoma and help to preserve muscle mass.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cancer-associated cachexia is a debilitating and potentially life-threatening syndrome characterized by progressive loss of body weight, skeletal muscle, and adipose tissue, leading to functional impairment and reduced response to oncologic therapy. It is driven in part by systemic inflammation and increased pro-inflammatory cytokines, and it cannot always be reversed with conventional support.

Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid (PUFA), has anti-inflammatory properties and is rapidly incorporated into cell membranes, modulating lipid mediator pathways. EPA supplementation may help to attenuate systemic inflammation, alleviate cachexia symptoms, and promote the production of specialized pro-resolving mediators. A daily dose of 3 grams appears sufficient to achieve maximal incorporation into cell membranes without significant adverse events.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with most patients diagnosed at advanced stages. Cachexia is common in advanced HCC and contributes to functional decline, increased treatment toxicity, and poorer outcomes. Preclinical studies suggest that omega-3 PUFAs may also exert anti-tumor effects through modulation of COX-2 and Wnt/beta-catenin signaling pathways.

For these reasons, in this proposal, the investigators aim to determine wheter supplementation with EPA in combination with chemotherapy will modify the blood profile of pro-inflammatory and pro-resolving mediators, promoting the resolution of inflammation associated with HCC, and, in turn, mitigate muscle mass loss during oncologic treatment.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Zaragoza
      • Zaragoza, Zaragoza, Spain, 50009
        • Hospital Clínico Universitario Lozano Blesa. IIS Aragón

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants diagnosed with unresectable HCC, candidates for systemic treatment with Sorafenib or similar agents.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Life expectancy > 8 weeks.
  • Not eligible for curative treatment (surgical resection/ablative therapy/liver transplantation).
  • Not having a history of previous or concomitant malignancy except when a disease-free interval > 5 years had been documented.
  • Not receiving any other systemic antitumor agents (docetaxel, doxorubicin, irinotecan).

Exclusion Criteria:

  • Allergy to omega-3 acid or fish-derived products.
  • Psychological or medical conditions that can interfere with study participation or the ability to provide informed consent.
  • Drug abuse (except for alcohol).
  • Any experimental therapy within 30 days prior to study entry.
  • Recurrent epistaxis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention group
Patients with unresectable hepatocellular carcinoma (HCC) were given 3 grams/day of an oral lipidic emulsion of eicosapentaenoic acid in addition to their oncologic care during 12 weeks.
Dietary supplement: Eicosapentaenoic acid oral lipidic emulsion
1 sachet/day of 20 ml containing 3g EPA during 12 weeks
Placebo Comparator: Control group
Patients with unresectable hepatocellular carcinoma (HCC) were given a placebo oral lipidic emulsion in addition to their oncologic care during 12 weeks.
Dietary supplement: Pacebo oral lipidic emulsion
1 sachet/day of 20 ml of placebo during 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of EPA supplementation on muscle mass
Time Frame: At baseline, and at 12 weeks (study completion)
Muscle mass is assessed by calculating the skeletal muscle index using computed tomography, based on a single axial slice at the L3 level. The SliceOmatic software (TomoVision) is used for the calculations. Sarcopenia is evaluated using two criteria: Carey reference values for end-stage liver disease patients awaiting transplantation, and Martin reference values for oncology patients.
At baseline, and at 12 weeks (study completion)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evolution of nutritional status.
Time Frame: At baseline, at 6 weeks, and at 12 weeks (study completion)
Nutritional status is assessed using the validated Patient-Generated Subjective Global Assessment tool (PG-SGA, Bauer 2002) that classify patients as well nourished (A), moderately malnourished or at risk of malnutrition (B), or severely malnourished (C).
At baseline, at 6 weeks, and at 12 weeks (study completion)
Effect of EPA supplementation on quality of life assessed using the EORTC-QLQ-30.
Time Frame: At baseline, at 6 weeks, and at 12 weeks (study completion)
Quality of life is assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30)
At baseline, at 6 weeks, and at 12 weeks (study completion)
Change in the quality of life assessed using the EORTC-QLQ-HCC18.
Time Frame: At baseline, at 6 weeks, and at 12 weeks (study completion)
Quality of life is assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (QLQ-HCC18).
At baseline, at 6 weeks, and at 12 weeks (study completion)
Effect of EPA supplementation on plasma and serum profiles of pro-inflammatory and pro-resolving lipid mediators.
Time Frame: At baseline, and at 12 weeks (study completion)
Plasma and serum concentrations of pro-inflammatory and pro-resolving lipid mediators derived from polyunsaturated fatty acids are determined using targeted LC-MS/MS.
At baseline, and at 12 weeks (study completion)
Change in C-reactive protein (CRP) concentration upon supplementation.
Time Frame: At baseline, and at 12 weeks (study completion)
The C-reactive protein is measured using an immunoturbidimetric assay following the standard laboratory methods in the Hospital Clínico Universitario Lozano Blesa.
At baseline, and at 12 weeks (study completion)
Change in interleukin 6 upon supplementation.
Time Frame: At baseline, and at 12 weeks (study completion)
Plasma IL-6 levels are determined by enzyme-linked immunosorbent assay.
At baseline, and at 12 weeks (study completion)
Change in interleukin 8 upon supplementation.
Time Frame: At baseline, and at 12 weeks (study completion)
Plasma Il-8 is quantified using the Human XL Cytokine Luminex® Kit Performance Assay (R&D Systems).
At baseline, and at 12 weeks (study completion)
Change in interferon gamma (IFNγ) upon supplementation.
Time Frame: At baseline, and at 12 weeks (study completion)
Plasma IFNγ is quantified using the Human XL Cytokine Luminex® Kit Performance Assay (R&D Systems).
At baseline, and at 12 weeks (study completion)
Change in the neutrophil-to-lymphocyte ratio (NLR) upon supplementation.
Time Frame: At baseline, and at 12 weeks (study completion)
NLR is calculated by dividing the absolute neutrophil count by the absolute lymphocyte count obtained from peripheral blood samples. Both values were derived from the complete blood count (CBC) analysis.
At baseline, and at 12 weeks (study completion)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto de Investigación Sanitaria Aragón

Collaborators

Solutex GC S.L.
Hospital Clínico Universitario Lozano Blesa

Investigators

  • Principal Investigator: Angel Lanas Arbeloa, MD, PhD, University Hospital Lozano Blesa. IIS Aragón. CIBER de Enfermedades Hepáticas y Digestivas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2019

Primary Completion (Actual)

September 17, 2023

Study Completion (Actual)

June 20, 2025

Study Registration Dates

First Submitted

May 8, 2026

First Submitted That Met QC Criteria

June 17, 2026

First Posted (Actual)

June 23, 2026

Study Record Updates

Last Update Posted (Actual)

June 23, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LMP225_18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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