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

Terminated

• Conditions: Refractory Ascites; Hepatic Hydrothorax; Cirrhosis; Hepatic Encephalopathy
• Interventions: Other: Oral glutamine challenge; Other: Psychometric Tests

• Registration Number: NCT02026609
• Lead Sponsor: University of Arkansas

Brief Summary

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.

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.

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-12-26
• Study First Submitted QC: 2014-01-02
• Study First Posted: 2014-01-03
• Primary Completion: 2015-01-27
• Study Completion: 2015-01-27
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-14
• Last Update Posted: 2017-04-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
TIPS	Psychometric Tests	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.
TIPS	Oral glutamine challenge	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.

Primary Outcome Measures

Name	Time	Method
Overt hepatic encephalopathy	up to 18 months	Classified according to West Haven criteria.

Secondary Outcome Measures

Name	Time	Method
Sarcopenia	Baseline and 6 months post-TIPS	According to CT scan L3 area of muscle mass
Physical activity	Baseline and 6 months post-TIPS	Pedometer readings and physical activity questionnaire
Dietary Intake	Baseline and 6 months post-TIPS	Food frequency questionnaire (FFQ, NutritionQuest, Berkeley, CA)

Trial Locations

Locations (3)

University of Montreal; 🇨🇦 Montreal, Quebec, Canada

University Hospitals of Geneva; 🇨🇭 Geneva, Switzerland

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States