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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03732586
Recruitment Status : Recruiting
First Posted : November 6, 2018
Last Update Posted : August 31, 2020
Sponsor:
Collaborator:
Universidad Nacional Autonoma de Mexico
Information provided by (Responsible Party):
Jacqueline Cordova-Gallardo, Hospital General Dr. Manuel Gea González

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Alcoholic Hepatitis Dietary Supplement: Omega 5 fatty acid supplement Other: PLACEBO Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Double-blind clinical trial.
Masking: Single (Participant)
Masking Description: Subjects will be randomly assigned to one of the two treatments. The randomization is done through a computer generated system. The labelling will be done by a pharmacist or similar. Envelopes with randomization listings will be stored in a secure environment within the Hospital. Blinding should be maintained throughout the study. The randomization code should not be broken during the course of the study unless it is necessary for the safety of the subjects, as judged by the investigator. The date, time and reason for unmasking must be recorded, along with the researcher's signature. The rupture of the study blind will be done once the database has been blocked. The study will be double-blind, which means that neither the patients nor the study site staff will have access to the randomization code until the code is broken.
Primary Purpose: Treatment
Official Title: Effect of Omega-5 Fatty Acid Supplement on Markers of Inflammation and Oxidative Stress in Patients With Severe Alcoholic Hepatitis Treated With Prednisone
Actual Study Start Date : September 30, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : December 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Prednisone

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 Name: placebo capsules




Primary Outcome Measures :
  1. 30 Day Survival [ Time Frame: day 30 ]
    Better survival in patients with omega 5 supplement associated to prednisone


Secondary Outcome Measures :
  1. 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)

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03732586


Contacts
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Contact: Jacqueline Cordova-Gallardo, MD +525540003000 jacquiemex2@yahoo.com.mx
Contact: Gabriela Gutierrez-Reyes, DSc 525556232673 gabgurey@yahoo.com

Locations
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Mexico
Laboratorio de Higado, Pancreas y Motilidad Intestinal. UNIVERSIDAD AUTONOMA DE MEXICO Recruiting
Mexico City, Cuauhtemoc, Mexico, 06720
Contact: Gabriela Gutierrez-Reyes, DSc    +525556232673    gabgurey@yahoo.com   
Principal Investigator: Gabriela Gutierrez-Reyes, DSc         
Sub-Investigator: Dorothy Rosique-Oramas, MS         
Sub-Investigator: Zaira Medina-Avila, MS         
Hospital General Dr. Manuel Gea Gonzalez Recruiting
Mexico City, Tlalpan, Mexico, 14080
Contact: Jacqueline Cordova-Gallardo, MD    525540003000 ext 1239    jacquiemex2@yahoo.com.mx   
Principal Investigator: Jacqueline Cordova-Gallardo, MD         
Sub-Investigator: Diana Munguia-Ramos, MD         
Sub-Investigator: Erika Karina Tenorio-Aguirre, MD         
Sub-Investigator: Paola Vazquez-Cardenas, DSc         
Sub-Investigator: Antonio Lopez-Gomez, MD         
Sub-Investigator: Yenisey Yadkinnie-Cruz, MD         
Sponsors and Collaborators
Hospital General Dr. Manuel Gea González
Universidad Nacional Autonoma de Mexico
Investigators
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Principal Investigator: Jacqueline Cordova-Gallardo, MD Hospital General Dr. Manuel Gea Gonzalez
Principal Investigator: Gabriela Gutierrez-Reyes, DSc Universidad Autonoma de México
Publications of Results:

Other Publications:

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Responsible Party: Jacqueline Cordova-Gallardo, Hepatologist, Hospital General Dr. Manuel Gea González
ClinicalTrials.gov Identifier: NCT03732586    
Other Study ID Numbers: Hospitalgea
First Posted: November 6, 2018    Key Record Dates
Last Update Posted: August 31, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The results will be shared in international medical meetings

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jacqueline Cordova-Gallardo, Hospital General Dr. Manuel Gea González:
Severe Alcoholic Hepatitis treatment
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis
Hepatitis, Alcoholic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders