Plasma Free Amino Acids in Patients With Hepatic Encephalopathy

Plasma Free Amino Acids in Patients With Hepatic Encephalopathy and Its Impact on Disease Outcomes.

This is study to investigate the plasma free amino acids profile in patients with decompensated liver cirrhosis and hepatic encephalopathy and its relation to the nutritional state of these patients.

• To investigate the plasma free amino acids relation to the nutritional state of patients with liver cirrhosis and hepatic encephalopathy.
• To determine the effectiveness, cost, cost-benefit and in-hospital prognosis of branched chain amino acid (BCAA) infusion as an adjuvant to conventional mainstay therapy in the treatment of hepatic encephalopathy due to liver cirrhosis.
• To determine the effectiveness of branched chain amino acid (BCAA) infusion on improving amino acid imbalance and Fischer ratio (Branched chain amino acids/Aromatic amino acids ratio).

Study Overview

• Status: Unknown
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: Aminoleban (8% amino acids infusion)

Detailed Description

Alterations in amino acid profiles observed in patients with liver cirrhosis are very specific and markedly differ from those observed in other disorders..

Until present time the treatment of hepatic encephalopathy is mainly aimed at reducing the production and intestinal absorption of ammonia by antibiotics and non-absorbable disaccharides, although the available data indicate a low success rate of these strategies.

Beneficial effects of branched chain amino acids supplementation (BCAA) may be more pronounced in patients with marked depression of BCAA and/or low Branched chain amino acids/Aromatic amino acids (BCAA/AAA) ratio in extracellular fluid.

It also may be suggested that the beneficial effect of long term intake of BCAA on hepatic encephalopathy demonstrated in clinical studies is related to improved muscle mass and nutritional status.

The current recommendation only includes oral BCAA to patients with liver disease who are intolerant to standard protein intake.

The rationale for this limitation is based on the fact that in the mentioned randomized trials, hepatic encephalopathy was not part of the inclusion criteria. Additionally, the positive effect was difficult to interpret as it was observed on compound end points, which combine survival, hospitalization, and cirrhosis complications. From these results, it is not possible to ascertain the role of BCAA in hepatic encephalopathy, which patients benefit and to what extent .

For this reason, the investigators designed this study to assess effectiveness of BCAA in improving clinical, nutritional and laboratory status of these patients.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: mahmoud HG Abdel-Rahman, specialist; Phone Number: +201003149449; Email: mahmoud_goda87@yahoo.com
• Study Contact Backup: Name: Sahar M Hassany, A.Professor; Phone Number: +201010431017; Email: saharhassany@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients known to be cirrhotic admitted at Al-Rajhi liver hospital at Assiut university by hepatic encephalopathy

Description

Inclusion Criteria:

• Patient has decompensated liver cirrhosis
• Patient has overt hepatic encephalopathy

Exclusion Criteria:

1. Protein losing enteropathy.

2. Neurological conditions that make the assessment of hepatic encephalopathy difficult

   1. Parkinson's disease
   2. Alzheimer's disease
   3. Concomitant stroke

3. Gastrointestinal Bleeding requiring blood transfusion

   -

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hepatic encephalopathy patients; The following will be administered to this group of patients rifaximin 550 tablets b.i.d Lactulose syrup 5cm b.i.d Enema b.i.d for 3 days
hepatic encephalopathy patients-amino; The following will be administered to this group of patients rifaximin 550 tablets b.i.d Lactulose syrup 5cm b.i.d Enema b.i.d plus Aminoleban (8% amino acids infusion) b.i.d for 3 days	Drug: Aminoleban (8% amino acids infusion); Each 1000ml of AMINOLEBAN contains: Aminoacetic acid - 9.0 g L-alanine -- 7.5 g L-arginine Hydrochloride (HCl) -- 7.3 g (L-arginine equivalent) -- (6.0 g) L-cysteine HCl monohydrate -- 0.4 g (L-cysteine equivalent) -- (0.3 g) L-histidine HCl monohydrate -- 3.2 g (L-histidine equivalent)-- (2.4 g) L-isoleucine -- 9.0 g L-leucine -- 11.0 g L-Lysine HCl -- 7.6 g (L-lysine equivalent) -- (6.1 g) L-methionine -- 1.0 g L-phenylalanine -- 1.0 g L-proline -- 8.0 g L-serine -- 5.0 g L-threonine -- 4.5 g L-tryptophan -- 0.7 g L-valine -- 8.4 g Water for injection q.s -- 1000 m

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amino acid profile in hepatic encephalopathy	Measuring the level of plasma different free amino acids in hepatic encephalopathy patients	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relation between amino acids and nutrition	Study the relation between amino acid profile and nutritional status of hepatic encephalopathy patients.	24 hours
IV Amino acids infusion effect	Investigating the prognosis and in-hospital mortality of patients with hepatic encephalopathy following the use of IV Amino acids infusion for 3 days	up to 1 week

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Chair: Ahmad H Salem, MD, Assiut University; Principal Investigator: Mahmoud HG Abdel-Rahman, Master, Assiut University; Study Director: Sahar M Hassany, Assiut University

Publications and helpful links

General Publications

• Als-Nielsen B, Gluud LL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ. 2004 May 1;328(7447):1046. doi: 10.1136/bmj.38048.506134.EE. Epub 2004 Mar 30.
• Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev. 2003;(2):CD001939. doi: 10.1002/14651858.CD001939.
• Charlton M. Branched-chain amino-acid granules: can they improve survival in patients with liver cirrhosis? Nat Clin Pract Gastroenterol Hepatol. 2006 Feb;3(2):72-3. doi: 10.1038/ncpgasthep0392. No abstract available.
• Dam G, Ott P, Aagaard NK, Vilstrup H. Branched-chain amino acids and muscle ammonia detoxification in cirrhosis. Metab Brain Dis. 2013 Jun;28(2):217-20. doi: 10.1007/s11011-013-9377-3. Epub 2013 Jan 15.
• Holecek M. Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy. Nutrition. 2015 Jan;31(1):14-20. doi: 10.1016/j.nut.2014.03.016. Epub 2014 Mar 30.
• Phongsamran PV, Kim JW, Cupo Abbott J, Rosenblatt A. Pharmacotherapy for hepatic encephalopathy. Drugs. 2010 Jun 18;70(9):1131-48. doi: 10.2165/10898630-000000000-00000.
• Wright G, Jalan R. Management of hepatic encephalopathy in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21(1):95-110. doi: 10.1016/j.bpg.2006.07.009.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 15, 2017
• Primary Completion (Anticipated): December 15, 2018
• Study Completion (Anticipated): February 15, 2019

Study Registration Dates

• First Submitted: October 5, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 11, 2017

Study Record Updates

• Last Update Posted (Actual): October 11, 2017
• Last Update Submitted That Met QC Criteria: October 10, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: plasma free amino acids
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: amino acids in liver cirrhosis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No