Effect of Omega 5 Fatty Acid as an Adyuvant Treatment to Prednisone in Patients With Severe Alcoholic Hepatitis
- Conditions
- Alcoholic Hepatitis
- Interventions
- Dietary Supplement: Omega 5 fatty acid supplementOther: PLACEBO
- Registration Number
- NCT03732586
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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 (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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Omega 5 fatty acid supplement 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 PLACEBO PLACEBO 20 patients will be assigned to traditional treatment (prednisone 40 mg per day) plus placebo
- Primary Outcome Measures
Name Time Method 30 Day Survival day 30 Better survival in patients with omega 5 supplement associated to prednisone
- Secondary Outcome Measures
Name Time Method Malondialdehyde serum levels 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.
Rate of reponse to steroids at day 7 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)
Oxidative Stress molecules serum levels 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.
Trial Locations
- Locations (2)
Hospital General Dr. Manuel Gea Gonzalez
🇲🇽Mexico City, Tlalpan, Mexico
Laboratorio de Higado, Pancreas y Motilidad Intestinal. UNIVERSIDAD AUTONOMA DE MEXICO
🇲🇽Mexico City, Cuauhtemoc, Mexico