Clinical trial NCT02026609: Glutamine Challenge as Predictor of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Official title: Glutamine Challenge as Predictor of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Refractory Ascites
Hepatic Hydrothorax
Hepatic Encephalopathy
Cirrhosis
Keywords: TIPS
Hepatic encephalopathy
Oral glutamine challenge
Psychometric tests
Portal hypertension
Cirrhosis
Lead sponsor: University of Arkansas
Sponsor class: OTHER
Collaborators: name: Université de Montréal
name: University Hospital, Geneva
First posted: 2014-01-03
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility 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.

Primary outcomes:
measure: Overt hepatic encephalopathy
timeFrame: up to 18 months
Secondary outcomes:
measure: Sarcopenia
timeFrame: Baseline and 6 months post-TIPS
measure: Physical activity
timeFrame: Baseline and 6 months post-TIPS
measure: Dietary Intake
timeFrame: Baseline and 6 months post-TIPS
Other outcomes:
measure: Skeletal muscle trophic factors
timeFrame: Baseline and 6 months post-TIPS
measure: Glutaminase gene variations
timeFrame: Baseline
measure: Psychometric tests
timeFrame: 3 and 6 months post-TIPS
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Montreal
country: Canada
facility: University of Montreal
state: Quebec
city: Geneva
country: Switzerland
facility: University Hospitals of Geneva
Study officials:
affiliation: University of Arkansas
name: Andres Duarte-Rojo, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rossle 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.
citation: Romero-Gomez M, Jover M, Del Campo JA, Royo JL, Hoyas E, Galan JJ, Montoliu C, Baccaro E, Guevara M, Cordoba J, Soriano G, Navarro JM, Martinez-Sierra C, Grande L, Galindo A, Mira E, Manes 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.
citation: Romero-Gomez 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. doi: 10.1016/s0168-8278(02)00330-6.
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.
citation: Duarte-Rojo A, Estradas J, Hernandez-Ramos R, Ponce-de-Leon S, Cordoba 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.
citation: 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. doi: 10.1111/j.1572-0241.2007.01048.x. Epub 2007 Jan 11.
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.