Clinical trial NCT03306498: Plasma Free Amino Acids in Patients With Hepatic Encephalopathy
Official title: Plasma Free Amino Acids in Patients With Hepatic Encephalopathy and Its Impact on Disease Outcomes.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatic Encephalopathy
Keywords: plasma free amino acids
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-10-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients known to be cirrhotic admitted at Al-Rajhi liver hospital at Assiut university by hepatic encephalopathy

Brief summary: 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).

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.

Eligibility criteria: 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

   -

Primary outcomes:
measure: Amino acid profile in hepatic encephalopathy
timeFrame: 24 hours
Secondary outcomes:
measure: Relation between amino acids and nutrition
timeFrame: 24 hours
measure: IV Amino acids infusion effect
timeFrame: up to 1 week
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Ahmad H Salem, MD
role: STUDY_CHAIR
affiliation: Assiut University
name: Mahmoud HG Abdel-Rahman, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Assiut University
name: Sahar M Hassany
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.