Effect of Omega 5 Fatty Acid as an Adyuvant Treatment to Prednisone in Patients With Severe Alcoholic Hepatitis
Effect of Omega-5 Fatty Acid Supplement on Markers of Inflammation and Oxidative Stress in Patients With Severe Alcoholic Hepatitis Treated With Prednisone
Lead Sponsor: Hospital General Dr. Manuel Gea González
Collaborator: Universidad Nacional Autonoma de Mexico
|Source||Hospital General Dr. Manuel Gea González|
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 treatment 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 this 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.
Double-blind clinical trial.
- GROUP A (standard treatment): Prednisone 40 mg a day + Placebo (manufactured by the same laboratory with the same presentation and physical appearance as the nanoemulsified pomegranate seed oil rich in Omega 5 fatty acid)
- GROUP B (combined treatment): Prednisone 40 mg per day + nanoemulsified 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 blinded 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 you 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, height, BMI), 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 mithocondrial 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 (parascentesis). 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 studies to be carried out. If they agree to participate, they will proceed to sign the informed consent of the patient and their family member. responsable. 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.
|Start Date||September 30, 2018|
|Completion Date||September 30, 2020|
|Primary Completion Date||March 30, 2020|
Intervention Type: Dietary Supplement
Intervention Name: Omega 5 fatty acid supplement
Description: 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.
Arm Group Label: Omega 5 fatty acid supplement
Intervention Type: Other
Intervention Name: PLACEBO
Description: 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.
Arm Group Label: PLACEBO
Other Name: placebo capsules
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, - 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.
- 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.
- Hepatorenal syndrome,
- 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.
Minimum Age: 18 Years
Maximum Age: 65 Years
Healthy Volunteers: No
Last Name: Jacqueline Cordova-Gallardo, MD
Email: [email protected]
Type: Principal Investigator
Investigator Affiliation: Hospital General Dr. Manuel Gea González
Investigator Full Name: Jacqueline Cordova-Gallardo
Investigator Title: Hepatologist
|Has Expanded Access||No|
|Number Of Arms||2|
Label: Omega 5 fatty acid supplement
Description: 20 patients will be assigned to traditional treatment with prednisone 40 mg per day plus dietary supplement with omega 5 fatty acid
Type: Placebo Comparator
Description: 20 patients will be assigned to traditional treatment (prednisone 40 mg per day) plus placebo
|Study Design Info||
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Double-blind clinical trial.
Primary Purpose: Treatment
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 labeling 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.