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

Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02026609
• Other study ID #: #135318
• Status: Terminated
• Phase: N/A
• First received: December 26, 2013
• Last updated: April 14, 2017
• Start date: May 2013
• Est. completion date: January 27, 2015

Study information

• Verified date: April 2017
• Source: University of Arkansas
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: January 27, 2015
• Est. primary completion date: January 27, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ascites
• Brain Diseases
• Cirrhosis
• Fibrosis
• Hepatic Encephalopathy
• Hepatic Hydrothorax
• Hydrothorax
• Refractory Ascites

Intervention

Other:
• Oral glutamine challenge
Blood ammonia determination before, 30-, 60-, and 90-minute, after intake of 10 g of L-glutamine
• Psychometric Tests
PHES (portosystemic hepatic encephalopathy score) and ICT (inhibitory control test)

Locations

Country	Name	City	State
Canada	University of Montreal	Montreal	Quebec
Switzerland	University Hospitals of Geneva	Geneva
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas

Sponsors (3)

Lead Sponsor	Collaborator
University of Arkansas	Université de Montréal, University Hospital, Geneva

Countries where clinical trial is conducted

United States,  Canada,  Switzerland, 

References & Publications (7)

Bajaj JS, Saeian K, Verber MD, Hischke D, Hoffmann RG, Franco J, Varma RR, Rao SM. Inhibitory control test is a simple method to diagnose minimal hepatic encephalopathy and predict development of overt hepatic encephalopathy. Am J Gastroenterol. 2007 Apr;102(4):754-60. Epub 2007 Jan 11. — View Citation

Ditisheim S, Giostra E, Burkhard PR, Goossens N, Mentha G, Hadengue A, Spahr L. A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis. BMC Gastroenterol. 2011 Dec 8;11:134. doi: 10.1186/1471-230X-11-134. — View Citation

Duarte-Rojo A, Estradas J, Hernández-Ramos R, Ponce-de-León S, Córdoba J, Torre A. Validation of the psychometric hepatic encephalopathy score (PHES) for identifying patients with minimal hepatic encephalopathy. Dig Dis Sci. 2011 Oct;56(10):3014-23. doi: 10.1007/s10620-011-1684-0. Epub 2011 Apr 3. — View Citation

Romero-Gómez M, Grande L, Camacho I, Benitez S, Irles JA, Castro M. Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J Hepatol. 2002 Dec;37(6):781-7. — View Citation

Romero-Gómez M, Jover M, Del Campo JA, Royo JL, Hoyas E, Galán JJ, Montoliu C, Baccaro E, Guevara M, Córdoba J, Soriano G, Navarro JM, Martínez-Sierra C, Grande L, Galindo A, Mira E, Mañes S, Ruiz A. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. Ann Intern Med. 2010 Sep 7;153(5):281-8. doi: 10.7326/0003-4819-153-5-201009070-00002. — View Citation

Rössle M, Gerbes AL. TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update. Gut. 2010 Jul;59(7):988-1000. doi: 10.1136/gut.2009.193227. — View Citation

Tandon P, Ney M, Irwin I, Ma MM, Gramlich L, Bain VG, Esfandiari N, Baracos V, Montano-Loza AJ, Myers RP. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl. 2012 Oct;18(10):1209-16. doi: 10.1002/lt.23495. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Skeletal muscle trophic factors	IGF-1 and myostatin levels	Baseline and 6 months post-TIPS
Other	Glutaminase gene variations	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	Baseline
Other	Psychometric tests	Repeat PHES and ICT	3 and 6 months post-TIPS
Primary	Overt hepatic encephalopathy	Classified according to West Haven criteria.	up to 18 months
Secondary	Sarcopenia	According to CT scan L3 area of muscle mass	Baseline and 6 months post-TIPS
Secondary	Physical activity	Pedometer readings and physical activity questionnaire	Baseline and 6 months post-TIPS
Secondary	Dietary Intake	Food frequency questionnaire (FFQ, NutritionQuest, Berkeley, CA)	Baseline and 6 months post-TIPS