<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03306498</url>
  </required_header>
  <id_info>
    <org_study_id>amino acids in liver cirrhosis</org_study_id>
    <nct_id>NCT03306498</nct_id>
  </id_info>
  <brief_title>Plasma Free Amino Acids in Patients With Hepatic Encephalopathy</brief_title>
  <official_title>Plasma Free Amino Acids in Patients With Hepatic Encephalopathy and Its Impact on Disease Outcomes.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is study to investigate the plasma free amino acids profile in patients with&#xD;
      decompensated liver cirrhosis and hepatic encephalopathy and its relation to the nutritional&#xD;
      state of these patients.&#xD;
&#xD;
        -  To investigate the plasma free amino acids relation to the nutritional state of patients&#xD;
           with liver cirrhosis and hepatic encephalopathy.&#xD;
&#xD;
        -  To determine the effectiveness, cost, cost-benefit and in-hospital prognosis of branched&#xD;
           chain amino acid (BCAA) infusion as an adjuvant to conventional mainstay therapy in the&#xD;
           treatment of hepatic encephalopathy due to liver cirrhosis.&#xD;
&#xD;
        -  To determine the effectiveness of branched chain amino acid (BCAA) infusion on improving&#xD;
           amino acid imbalance and Fischer ratio (Branched chain amino acids/Aromatic amino acids&#xD;
           ratio).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alterations in amino acid profiles observed in patients with liver cirrhosis are very&#xD;
      specific and markedly differ from those observed in other disorders..&#xD;
&#xD;
      Until present time the treatment of hepatic encephalopathy is mainly aimed at reducing the&#xD;
      production and intestinal absorption of ammonia by antibiotics and non-absorbable&#xD;
      disaccharides, although the available data indicate a low success rate of these strategies.&#xD;
&#xD;
      Beneficial effects of branched chain amino acids supplementation (BCAA) may be more&#xD;
      pronounced in patients with marked depression of BCAA and/or low Branched chain amino&#xD;
      acids/Aromatic amino acids (BCAA/AAA) ratio in extracellular fluid.&#xD;
&#xD;
      It also may be suggested that the beneficial effect of long term intake of BCAA on hepatic&#xD;
      encephalopathy demonstrated in clinical studies is related to improved muscle mass and&#xD;
      nutritional status.&#xD;
&#xD;
      The current recommendation only includes oral BCAA to patients with liver disease who are&#xD;
      intolerant to standard protein intake.&#xD;
&#xD;
      The rationale for this limitation is based on the fact that in the mentioned randomized&#xD;
      trials, hepatic encephalopathy was not part of the inclusion criteria. Additionally, the&#xD;
      positive effect was difficult to interpret as it was observed on compound end points, which&#xD;
      combine survival, hospitalization, and cirrhosis complications. From these results, it is not&#xD;
      possible to ascertain the role of BCAA in hepatic encephalopathy, which patients benefit and&#xD;
      to what extent .&#xD;
&#xD;
      For this reason, the investigators designed this study to assess effectiveness of BCAA in&#xD;
      improving clinical, nutritional and laboratory status of these patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 15, 2017</start_date>
  <completion_date type="Anticipated">February 15, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Amino acid profile in hepatic encephalopathy</measure>
    <time_frame>24 hours</time_frame>
    <description>Measuring the level of plasma different free amino acids in hepatic encephalopathy patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relation between amino acids and nutrition</measure>
    <time_frame>24 hours</time_frame>
    <description>Study the relation between amino acid profile and nutritional status of hepatic encephalopathy patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IV Amino acids infusion effect</measure>
    <time_frame>up to 1 week</time_frame>
    <description>Investigating the prognosis and in-hospital mortality of patients with hepatic encephalopathy following the use of IV Amino acids infusion for 3 days</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Hepatic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>hepatic encephalopathy patients</arm_group_label>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hepatic encephalopathy patients-amino</arm_group_label>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aminoleban (8% amino acids infusion)</intervention_name>
    <description>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</description>
    <arm_group_label>hepatic encephalopathy patients-amino</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients known to be cirrhotic admitted at Al-Rajhi liver hospital at Assiut university by&#xD;
        hepatic encephalopathy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient has decompensated liver cirrhosis&#xD;
&#xD;
          -  Patient has overt hepatic encephalopathy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Protein losing enteropathy.&#xD;
&#xD;
          2. Neurological conditions that make the assessment of hepatic encephalopathy difficult&#xD;
&#xD;
               1. Parkinson's disease&#xD;
&#xD;
               2. Alzheimer's disease&#xD;
&#xD;
               3. Concomitant stroke&#xD;
&#xD;
          3. Gastrointestinal Bleeding requiring blood transfusion&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmad H Salem, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mahmoud HG Abdel-Rahman, Master</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sahar M Hassany</last_name>
    <role>Study Director</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>mahmoud HG Abdel-Rahman, specialist</last_name>
    <phone>+201003149449</phone>
    <email>mahmoud_goda87@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sahar M Hassany, A.Professor</last_name>
    <phone>+201010431017</phone>
    <email>saharhassany@yahoo.com</email>
  </overall_contact_backup>
  <reference>
    <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>
    <PMID>15054035</PMID>
  </reference>
  <reference>
    <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>
    <PMID>12804416</PMID>
  </reference>
  <reference>
    <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>
    <PMID>16456570</PMID>
  </reference>
  <reference>
    <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>
    <PMID>23315357</PMID>
  </reference>
  <reference>
    <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>
    <PMID>25220875</PMID>
  </reference>
  <reference>
    <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>
    <PMID>20518580</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>17223499</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 5, 2017</study_first_submitted>
  <study_first_submitted_qc>October 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>October 10, 2017</last_update_submitted>
  <last_update_submitted_qc>October 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Mahmoud Hamed Goda</investigator_full_name>
    <investigator_title>Specialist</investigator_title>
  </responsible_party>
  <keyword>plasma free amino acids</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatic Encephalopathy</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03306498
org study id: amino acids in liver cirrhosis
nct id: NCT03306498
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
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).
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.
observational model: Cohort
time perspective: Prospective
measure: Amino acid profile in hepatic encephalopathy
time frame: 24 hours
description: Measuring the level of plasma different free amino acids in hepatic encephalopathy patients
measure: Relation between amino acids and nutrition
time frame: 24 hours
description: Study the relation between amino acid profile and nutritional status of hepatic encephalopathy patients.
measure: IV Amino acids infusion effect
time frame: up to 1 week
description: Investigating the prognosis and in-hospital mortality of patients with hepatic encephalopathy following the use of IV Amino acids infusion for 3 days
arm group label: hepatic encephalopathy patients
description: 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
arm group label: hepatic encephalopathy patients-amino
description: 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
intervention type: Drug
intervention name: Aminoleban (8% amino acids infusion)
description: 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
arm group label: hepatic encephalopathy patients-amino
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ahmad H Salem, MD
role: Study Chair
affiliation: Assiut University
last name: Mahmoud HG Abdel-Rahman, Master
role: Principal Investigator
affiliation: Assiut University
last name: Sahar M Hassany
role: Study Director
affiliation: Assiut University
last name: mahmoud HG Abdel-Rahman, specialist
phone: +201003149449
email: mahmoud_goda87@yahoo.com
last name: Sahar M Hassany, A.Professor
phone: +201010431017
email: saharhassany@yahoo.com
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.
PMID: 15054035
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.
PMID: 12804416
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.
PMID: 16456570
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.
PMID: 23315357
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.
PMID: 25220875
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.
PMID: 20518580
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.
PMID: 17223499
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Mahmoud Hamed Goda
investigator title: Specialist
mesh term: Hepatic Encephalopathy
mesh term: Brain Diseases