Plasma Free Amino Acids in Patients With Hepatic Encephalopathy

Hepatic Encephalopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03306498
• Other study ID #: amino acids in liver cirrhosis
• Status: Not yet recruiting
• Phase: N/A
• First received: October 5, 2017
• Last updated: October 10, 2017
• Start date: December 15, 2017
• Est. completion date: February 15, 2019

Study information

• Verified date: October 2017
• Source: Assiut University
• Contact: mahmoud HG Abdel-Rahman, specialist
• Phone: +201003149449
• Email: mahmoud_goda87[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: February 15, 2019
• Est. primary completion date: December 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (7)

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. Epub 2004 Mar 30. Review. — View Citation

Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev. 2003;(2):CD001939. Review. Update in: Cochrane Database Syst Rev. 2015;2:CD001939. — View 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. — View 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. Review. — View 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. Review. — View 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. Review. — View Citation

Wright G, Jalan R. Management of hepatic encephalopathy in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21(1):95-110. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amino acid profile in hepatic encephalopathy	Measuring the level of plasma different free amino acids in hepatic encephalopathy patients	24 hours
Secondary	Relation between amino acids and nutrition	Study the relation between amino acid profile and nutritional status of hepatic encephalopathy patients.	24 hours
Secondary	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