Glutamine Challenge as Predictor of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Arkansas
Sponsor:
Collaborators:
Université de Montréal
University Hospital, Geneva
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT02026609
First received: December 26, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

Transjugular intrahepatic portosystemic shunt (TIPS) is the first-line therapy for patients with cirrhosis and refractory ascites. However, mental changes known as hepatic encephalopathy (HE) frequently occur after TIPS. There is no effective method to predict HE after TIPS. Oral glutamine challenge (OGC) and psychometric tests have been used to assess the risk for HE, but never in patients undergoing TIPS. Severe muscle loss may also predispose patients to HE. The aim of the present study is to assess if both the OGC and psychometric tests can accurately predict the development of overt HE after TIPS. Patients will be studied before TIPS and followed after TIPS for the development of HE. The role of muscle loss in favoring HE, as well as is possible reversibility after TIPS will also be investigated.


Condition Intervention
Refractory Ascites
Hepatic Hydrothorax
Hepatic Encephalopathy
Cirrhosis
Other: Oral glutamine challenge
Other: Psychometric Tests

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Glutamine Challenge as Predictor of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Overt hepatic encephalopathy [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
    Classified according to West Haven criteria.


Secondary Outcome Measures:
  • Sarcopenia [ Time Frame: Baseline and 6 months post-TIPS ] [ Designated as safety issue: No ]
    According to CT scan L3 area of muscle mass

  • Physical activity [ Time Frame: Baseline and 6 months post-TIPS ] [ Designated as safety issue: No ]
    Pedometer readings and physical activity questionnaire

  • Dietary Intake [ Time Frame: Baseline and 6 months post-TIPS ] [ Designated as safety issue: No ]
    Food frequency questionnaire (FFQ, NutritionQuest, Berkeley, CA)


Other Outcome Measures:
  • Skeletal muscle trophic factors [ Time Frame: Baseline and 6 months post-TIPS ] [ Designated as safety issue: No ]
    IGF-1 and myostatin levels

  • Glutaminase gene variations [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Genetic variations in the glutaminase gene (located at 2q-32-134) consisting of single nucleotide polymorphisms (SNPs) identifying a microsatellite of GCA repeats in the 5' untranslated region

  • Psychometric tests [ Time Frame: 3 and 6 months post-TIPS ] [ Designated as safety issue: No ]
    Repeat PHES and ICT


Biospecimen Retention:   Samples With DNA

Serum, plasma, and PBMCs


Estimated Enrollment: 220
Study Start Date: May 2013
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
TIPS
Patients 18-75 year old with refractory ascites or hepatic hydrothorax and cirrhosis, eligible for TIPS placement. All patients will have a baseline oral glutamine challenge and psychometric tests.
Other: Oral glutamine challenge
Blood ammonia determination before, 30-, 60-, and 90-minute, after intake of 10 g of L-glutamine
Other: Psychometric Tests
PHES (portosystemic hepatic encephalopathy score) and ICT (inhibitory control test)

Detailed Description:

In cirrhosis, up to 10% of patients develop refractory ascites. TIPS (transjugular intrahepatic portosystemic shunt) is the first-line therapy for these patients. However, 30% will go on to develop hepatic encephalopathy (HE) as a consequence of TIPS, and there is no effective method to predict this outcome. Oral glutamine challenge (OGC) is used to functionally assess ammonia metabolism, and the severity of porto-systemic collateralization, and it has been used to predict overt HE. Psychometric tests (i.e. Psychometric Hepatic Encephalopathy Score [PHES] and inhibitory control test) allow the identification of covert forms of HE and can also predict overt HE. Severe sarcopenia may also predispose patients to HE. The aim of the present study is to assess if both the degree of impairment in ammonia metabolism as estimated with the OGC, and cognitive status as determined by psychometric tests, can accurately predict the development of overt HE after TIPS. Patients will be studied before TIPS and followed after TIPS for the development of overt HE. The role of sarcopenia in favoring HE, as well as is possible reversibility after TIPS will also be investigated.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Consecutive patients will be recruited from the Gastroenterology / Hepatology Clinics at UAMS and other participating centers. Those fulfilling inclusion/exclusion criteria will be invited to participate.

Criteria

Inclusion Criteria:

  • Cirrhosis (any etiology)
  • Refractory ascites or hepatic hydrothorax and plan for TIPS placement

Exclusion Criteria:

  • Well-documented overt hepatic encephalopathy, either persistent or at the time of screening
  • Any contraindication for TIPS placement

    • Except for coagulopathy and thrombocytopenia (decided on an individual basis)
  • Uncontrolled depression/anxiety disorder or use of antipsychotic drugs
  • Active use of alcohol or illicit drugs
  • History of dementia
  • TIPS planned for another indication.
  • Active alcoholic liver disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02026609

Contacts
Contact: Andres Duarte-Rojo, MD, MSc 501.686.5175 aduarterojo@uams.edu
Contact: Jonathan A Dranoff, MD 501.686.5175 jadranoff@uams.edu

Locations
United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Andres Duarte-Rojo, MD, MSc    501-686-5175    aduarterojo@uams.edu   
Contact: Jonathan A Dranoff, MD    501.686.5175    jadranoff@uams.edu   
Sub-Investigator: Matthew G Deneke, MD         
Sub-Investigator: James C Meek, MD         
Sub-Investigator: Jonathan A Dranoff, MD         
Principal Investigator: Andres Duarte-Rojo, MD, MSc         
Canada, Quebec
University of Montreal Not yet recruiting
Montreal, Quebec, Canada, H2X 1P1
Contact: Christopher F Rose, PhD    514-890-8000 ext 35740    christopher.rose@umontreal.ca   
Principal Investigator: Christopher F Rose, PhD         
Switzerland
University Hospitals of Geneva Not yet recruiting
Geneva, Switzerland
Contact: Laurent Spahr, MD    +41223729340    Laurent.Spahr@hcuge.ch   
Principal Investigator: Laurent Spahr, MD, MPH         
Sponsors and Collaborators
University of Arkansas
Université de Montréal
University Hospital, Geneva
Investigators
Principal Investigator: Andres Duarte-Rojo, MD, MSc University of Arkansas
  More Information

Publications:

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT02026609     History of Changes
Other Study ID Numbers: #135318
Study First Received: December 26, 2013
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arkansas:
TIPS
Hepatic encephalopathy
Oral glutamine challenge
Psychometric tests
Portal hypertension
Cirrhosis

Additional relevant MeSH terms:
Hepatic Encephalopathy
Brain Diseases
Hydrothorax
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Metabolic Diseases
Pleural Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 01, 2014