To Study the Immunomodulating Effects and Safety Profile of ω3 and ω6 PUFA Containing Intravenous Lipid Emulsion in Patients With Acute on Chronic Liver Failure

Study Overview
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Brief Summary
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Study population: Patients admitted or seen in OPD (Out Patient Department), Department of Hepatology. Study design- Prospective Randomized Controlled Trial. Study period-January 2016 to May 2017 Intervention- Subjects will be randomized into 3 groups Group A subjects will receive ω3 PUFA (Polyunsaturated Fatty Acids) (10% Omegavan 100 ml). Group B- will receive ω6 PUFA (Polyunsaturated Fatty Acids) (10% Intralipid 100 ml). Group C -Placebo group Monitoring and assessment- :- The following tests will be done in these patients:- Complete clinical examination. Serum electrolytes- sodium, potassium, calcium, magnesium, phosphate levels BUN (Blood Urea Nitrogen) Serum free fatty acid levels Lipid profile. Arterial ammonia Arterial lactate Blood sugar and serum insulin levels

Official Title
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To Study the Immunomodulating Effects and Safety Profile of ω3 and ω6 PUFA Containing Intravenous Lipid Emulsion in Patients With Acute on Chronic Liver Failure

Conditions
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Chronic Liver Failure

Intervention / Treatment
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* Drug: ω3 PUFA (Polyunsaturated fatty acids) (10% Omegavan 100 ml)
* Drug: ω6 PUFA (Polyunsaturated fatty acids) (10% Intralipid 100 ml)
* Drug: No Lipid Emulsion/Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute on Chronic Liver Failure (ACLF) patients aged 18 years and above Patients tolerating enteral nutrition Patients with no overt sepsis - no fever, sterile blood and urine cultures, procalcitonin <2 Exclusion Criteria: Active ongoing GI bleed Allergy to soya oil, eggs, peanuts or other ingredients of intralipid. Co-morbidities like Diabetes mellitus, hyperlipidemia, CAD and hypothyroidism. Renal failure (S.creatinine > 2.5mg%) Pregnancy Patients with shock requiring vasopressor support Patients on anticoagulants Refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ω3 PUFA(10% Omegavan 100 ml)<br> | Drug: ω3 PUFA (Polyunsaturated fatty acids) (10% Omegavan 100 ml)<br> <br> |
| Experimental: ω6 PUFA (20% Intralipid 50 ml)<br> | Drug: ω6 PUFA (Polyunsaturated fatty acids) (10% Intralipid 100 ml)<br> <br> |
| Placebo Comparator: Placebo Arm<br>No Lipid Emulsion will be given in this arm | Drug: No Lipid Emulsion/Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of intravenous lipid emulsions (w3/ w6) on systemic inflammation and endotoxemia levels at the end of 5 days. | Decrease in endotoxins levels , TNF alpha,ilnterleukin 6,ilnterleukin 10,Monocyte/ macrophage activation etc. All of them are markers of inflammation. The outcome systemic inflammation is a composite outcome which includes all the above mentioned markers | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of sepsis and related complications |  | 28 days | 
| Effect of lipid infusion (w3/w6) on metabolic parameters viz., serum triglyceride levels, serum ketone levels, free fatty acid levels and arterial lactate levels. | Metabolic parameter is a composite outcome of all the above said markers. | 5 days | 
| Influence of lipid infusion (w3/w6) on nitrogen balance. | Improvement or deterioration in urinary urea nitrogen. | 5 days | 
| Effect of lipid infusion (w3/w6) on International Normalized Ratio (INR). | Effect is defined as INR (International Normalized Ratio) value within normal limit or improvement as compare to baseline value. | 5 days | 
| Oxidative stress response to lipid infusion | Oxidative stress response is based on the Improvement or deterioration in Isoprostane levels in urine | 5 days | 
| Influence of lipid infusion(w3/w6) on 28day mortality |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute