Effect of Omega 5 Fatty Acid as an Adyuvant Treatment to Prednisone in Patients With Severe Alcoholic Hepatitis

May 22, 2023 updated by: Jacqueline Cordova-Gallardo, Hospital General Dr. Manuel Gea González

Effect of Omega-5 Fatty Acid Supplement on Markers of Inflammation and Oxidative Stress in Patients With Severe Alcoholic Hepatitis Treated With Prednisone

In Mexico, alcoholic liver disease is the fourth cause of mortality (INEGI). Patients with severe alcoholic hepatitis have a high mortality at 28 days and 6 months, patients receiving standard therapy with prednisone that are non responders (Lille> 0.45) have a survival of 53.3 ± 5.1 % to 28 days. At present, there is not a completely effective treatment for non responders patients, with a high mortality, so it is necessary to look for other therapeutic strategies.

The omega-5 fatty acid (punicic acid) has been considered a powerful antioxidant, it is an agonist of PPAR gamma, has been shown to reduce lipid peroxidation, and restore levels of antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. It has also been shown to inhibit the expression of proinflammatory cytokines (such as IL6, IL8, IL23, IL12 and TNFalpha) through PPAR and modulation delta.

The objective of this study is to evaluate the effect of Omega 5 fatty acid on inflammatory markers and antioxidant-oxidant balance markers in patients with severe alcoholic hepatitis treated with prednisone. HYPOTHESIS. Omega 5 fatty acid being a PPARgamma agonist reduces lipid peroxidation and protein damage, restoring reduced glutathione levels, as well as decreasing proinflammatory cytokines, in patients with Severe Alcoholic Hepatitis treated with prednisone and supplementation with fatty acid Omega 5.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Double-blind clinical trial.

Two groups:

  • GROUP A (standard treatment): Prednisone 40 mg a day + Placebo (manufactured by the same laboratory with the same presentation and physical appearance as the nanoemulsifyied pomegranate seed oil rich in Omega 5 fatty acid)
  • GROUP B (combined treatment): Prednisone 40 mg per day + nanoemulsifiyied pomegranate seed oil rich in Omega 5 fatty acid (2 capsules of 0.64g each / day).

STUDY UNIVERSE: Patients> 18 years old, indistinct gender, with a diagnosis of severe alcoholic hepatitis.

STUDY POPULATION: Patients with clinical and laboratory diagnosis of alcoholic hepatitis Severe Maddrey score ≥32.

SAMPLE SIZE: Double-blind clinical trial, which will include 20 patients for standard treatment and 20 patients for combined treatment, patients who meet the inclusion criteria will be invited to participate. If they agree to participate (after signing the informed consent), the AUDIT C and CAGE questionnaires will be applied, as well as the measurement of anthropometric values and the taking of 3 blood tubes (2 purple and 1 yellow) for the measurement of cytokines, markers of oxidative stress, lipid peroxidation and protein carbonyls.

The initial evaluation will include liver ultrasound, heart rate, blood pressure, temperature, anthropometric evaluation (weight (kilograms), height (meters), BMI (kg/m2), evaluation of ascites (abdominal circumference), hepatic encephalopathy (West Haven Scale). Alcohol abuse will be assessed using the AUDIT and CAGE score. Start-up laboratories will be carried out: TP, INR, Complete liver function tests (BT, BD, FA, AST, ALT, GGT, Albumin), Seric electrolytes (Na, K, Phosphorus, Magnesium), Creatinine, Blood cytometry (Leukocytes (PMN) ), hemoglobin, VCM, platelets), lipid profile (ColT, HDL, LDL, TGs), ferritin and transferrin saturation, Anti-nuclear antibodies, Anti mithochondrial antibodies, AgHBs, AcHBc, anti HCV, anti HIV. The scrutiny of bacterial infections will be carried out through urine culture, blood cultures and in case of suspicion of SBP (paracenthesis). Child-Pugh score (A5-6, B7-9, C10-12), Maddrey score, MELD, ABIC score, Glasgow score. Chest x-Ray, General Urine Test.

Patients who meet the inclusion criteria, previously described, will be proposed to participate in the study, explaining in detail the procedures as well as the studiesthat will be performed. If they agree to participate, they will proceed to the signature of the informed consent by the patient and their responsible family member. Samples (2 yellow tubes and 2 purple tubes) will be taken for the measurement of cytokines, markers of oxidative stress, lipid peroxidation and protein carbonyls prior to the supply of the supplement vs placebo as well as the start of standard treatment. It will be explained to the patient that these samples will be done in 4 times (at diagnosis, on day 7, 14 and 28), which will be carried out during their hospitalization and follow-up.

Both treatments will be taken for 28 days.

Study Type

Interventional

Enrollment (Actual)

40

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 Contact

Study Contact Backup

  • Name: Gabriela Gutierrez-Reyes, DSc
  • Phone Number: 525556232673
  • Email: gabgurey@yahoo.com

Study Locations

  • Mexico
    • Cuauhtemoc
      • Mexico City, Cuauhtemoc, Mexico, 06720
        • Laboratorio de Higado, Pancreas y Motilidad Intestinal. UNIVERSIDAD AUTONOMA DE MEXICO
    • Tlalpan
      • Mexico City, Tlalpan, Mexico, 14080
        • Hospital General Dr. Manuel Gea Gonzalez

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with clinical and biochemical criteria for severe alcoholic hepatitis (Total bilirubin greater than 5 mg/dl in absence of biliary tract obstruction evidenced by ultrasound)
  • history of chronic alcohol intake (greater than 50 g / day for at least 3 months),
  • leukocytosis (neutrophilia)
  • elevation of transaminases with an aspartate aminotransferase / alanine aminotransferase ratio equal or greater than 2)
  • discriminant function greater than 32.

Exclusion Criteria:

  • Hepatorenal syndrome (serum creatinine >2.5mg/dl)
  • Hepatocellular carcinoma.
  • Hepatitis C virus, hepatitis B virus or human immunodeficiency virus infection.
  • Cancer, heart disease, neurological or severe neurological.
  • Patients taking pentoxifylline, steroids, S-adenosyl L- methionine or N-Acetylcysteine.

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Omega 5 fatty acid supplement
20 patients will be assigned to traditional treatment with prednisone 40 mg per day plus dietary supplement with omega 5 fatty acid
Dietary supplement: Omega 5 fatty acid supplement
Patients will be randomized to receive traditional treatment (prednisone 40 mg per day) plus omega 5 fatty acid ( 2 capsules of 0.64g per day) for 28 days.
Placebo Comparator: PLACEBO
20 patients will be assigned to traditional treatment (prednisone 40 mg per day) plus placebo
Other: PLACEBO
Patients will be randomized to receive the traditional treatment (prednisone 40 mg per day) plus placebo (2 capsules of placebo with identical appereance and size like omega 5 supplement) for 28 days.
Other Names:
  • placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30 Day Survival
Time Frame: day 30
Better survival in patients with omega 5 supplement associated to prednisone
day 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of reponse to steroids at day 7
Time Frame: day 7
To describe the response to steroids (Lille score) at 7 days of treatment in patients with severe alcoholic hepatitis with combined treatment (Omega 5 and steroids) compared to standard treatment. (Lille response describe a below of 0.45)
day 7
Malondialdehyde serum levels
Time Frame: basal, day 7, day 14 and day 28
To determine the serum concentrations of lipid peroxidation molecules (malondialdehyde (MDA expressed in mM) in patients with severe alcoholic hepatitis treated with prednisone compare to those treated with prednisona and omega5.
basal, day 7, day 14 and day 28
Oxidative Stress molecules serum levels
Time Frame: basal, day 7, day 14 and day 28
To assess changes in oxidative stress markers (Oxidative glutation and reduced glutation expressed in mM) in patients with severe alcoholic hepatitis treated with prednisone compared to those treated with prednisone and omega 5.
basal, day 7, day 14 and day 28

Collaborators and Investigators

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

Sponsor

Hospital General Dr. Manuel Gea González

Collaborators

Universidad Nacional Autonoma de Mexico

Investigators

  • Principal Investigator: Jacqueline Cordova-Gallardo, MD, Hospital General Dr. Manuel Gea Gonzalez
  • Principal Investigator: Gabriela Gutierrez-Reyes, DSc, Universidad Autonoma de México

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)

September 30, 2018

Primary Completion (Actual)

January 1, 2023

Study Completion (Actual)

May 22, 2023

Study Registration Dates

First Submitted

October 30, 2018

First Submitted That Met QC Criteria

November 5, 2018

First Posted (Actual)

November 6, 2018

Study Record Updates

Last Update Posted (Actual)

May 23, 2023

Last Update Submitted That Met QC Criteria

May 22, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Hospitalgea

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The results will be shared in international medical meetings

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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