Efficacy of Lactoferrin as an Adjunct Therapy in Patients With Hepatic Encephalopathy

Study Overview
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Brief Summary
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The aim of this study is to evaluate the efficacy of lactoferrin as an adjunct therapy in improving clinical symptoms and laboratory indices in individuals with hepatic encephalopathy.

Detailed Description
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Nonabsorbable disaccharides, such as lactulose or lactitol, decrease the absorption of ammonia and are considered a first-line treatment for hepatic encephalopathy. Antimicrobial therapy also is a part of treatment regimen to alter the gut microbiota to create a more favorable microbiome that results in lower endogenous bacterial production of ammonia and Rifaximin is now the preferred antimicrobial agent for the treatment of hepatic encephalopathy. Many researchers have focused on identifying promising therapeutics and prebiotics in the hope of improving the treatment of hepatic encephalopathy, therefore there is a need to add an adjuvant therapy to decrease oxidative stress and pro-inflammatory cytokines.

Official Title
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Efficacy of Lactoferrin as an Adjunct Therapy in Patients With Hepatic Encephalopathy

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: Lactoferrin Bovine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years and older. Grade I and II hepatic encephalopathy. Exclusion Criteria: Pregnant and breastfeeding women. Grade III and IV hepatic encephalopathy. Individuals confirmed to be allergic to milk protein

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: It is a randomized controlled clinical trial (Pilot study) that will be conducted on hepatic encephalopathy patients who will attend to National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt to receive the treatment regimen in concurrence with the Egyptian guidelines of treatment. Eligible patients will randomly assigned in a 1:1:1 ratio to receive lactoferrin (Pravotin@ sachets) as followings: Group I: Patients receive standard care alone (control group) Group II: Patients receive 100mg lactoferrin orally (one sachet (100 mg), one time a day) plus standard care. Group III: Patients receive 200 mg lactoferrin orally (one sachet (100mg), two times a day) plus standard care. Lactoferrin will be administrated in groups II and III for 15 days. The blood samples of all eligible participants and reported signs and symptoms will be collected after 15 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lactoferrin bovine once a day<br>15 patients will be subjected to take 100mg of lactoferrin bovine in the form of sachets twice per day for 15 days. | Drug: Lactoferrin Bovine<br>* Lactoferrin bovine with concentration 100 mg will be given to the patients in test groups in the form of sachets.<br>* Other names: Pravotin sachets 100 mg;|
| Active Comparator: Lactoferrin bovine twice a day<br>15 patients will be subjected to take 100mg of lactoferrin bovine in the form of sachets once per day for 15 days. | Drug: Lactoferrin Bovine<br>* Lactoferrin bovine with concentration 100 mg will be given to the patients in test groups in the form of sachets.<br>* Other names: Pravotin sachets 100 mg;|
| No Intervention: Control group<br>15 patients will be subjected to take only the standard treatment regimen that is applied at the National hepatology and tropical medicine research institute in Egypt. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum concentration of inflammatory cytokines | Change in serum concentration of inflammatory cytokine Tumor necrosis factor-alpha (TNF-a) (pg/ml) | 15 days | 
| Change in serum concentration of Nuclear factor kB | Change in serum concentration of Nuclear factor kB (NFkB) (ng/ml) | 15 days | 
| Change in serum concentration of oxidative stress markers | Change in serum concentration of oxidative stress markers Malondialdehyde (MDA) (n.mol/mg/protein) and Glutathione (GSH) (m.mol/mg/protein) | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Psychometric Hepatic Encephalopathy Score (PHES) | Number connection test A (NCT-A) - in this test the numbers have to be joined consecutively in ascending numerical order (1, 2, 3…) as quickly as possible. | 15 days | 
| Change in Psychometric Hepatic Encephalopathy Score (PHES) | Digit symbol test (DST) - in this test the patient is given a series of double-boxes with a number given in the upper part. The task is to draw a symbol pertinent to this number into the lower part of the boxes. Nine fixed pairs of numbers and symbols are given at the top of the test sheet. Test result is the number of boxes correctly filled within 90 seconds. | 15 days | 
| Change in Psychometric Hepatic Encephalopathy Score (PHES) | Simplified animal naming test (S-ANT) - in this test patients are asked to name as many animals as possible in one minute. Repeats and errors were excluded from the calculation. The number of named animals after one minute was the definitive score. | 15 days | 
| Length of hospital stay | Length of hospital stay | 15 days | 
| The rate of adverse events occurring during the treatment | Number of patients who experienced adverse events such as diarrhea, rash, loss of appetite, fatigue, and constipation. | 15 days | 
| Number of patients transferred to ICU | Number of patients transferred to ICU | 15 days |