NCT02026609

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started May 2013

Geographic Reach
3 countries

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2013

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

December 26, 2013

Completed
8 days until next milestone

First Posted

Study publicly available on registry

January 3, 2014

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 27, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2015

Completed
Last Updated

April 17, 2017

Status Verified

April 1, 2017

Enrollment Period

1.7 years

First QC Date

December 26, 2013

Last Update Submit

April 14, 2017

Conditions

Refractory AscitesHepatic HydrothoraxHepatic EncephalopathyCirrhosis

Keywords

TIPSHepatic encephalopathyOral glutamine challengePsychometric testsPortal hypertensionCirrhosis

Outcome Measures

Primary Outcomes (1)

  • Overt hepatic encephalopathy

    Classified according to West Haven criteria.

    up to 18 months

Secondary Outcomes (3)

  • Sarcopenia

    Baseline and 6 months post-TIPS

  • Physical activity

    Baseline and 6 months post-TIPS

  • Dietary Intake

    Baseline and 6 months post-TIPS

Other Outcomes (3)

  • Skeletal muscle trophic factors

    Baseline and 6 months post-TIPS

  • Glutaminase gene variations

    Baseline

  • Psychometric tests

    3 and 6 months post-TIPS

Study Arms (1)

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 challengeOther: Psychometric Tests

Interventions

Oral glutamine challengeOTHER

Blood ammonia determination before, 30-, 60-, and 90-minute, after intake of 10 g of L-glutamine

TIPS
Psychometric TestsOTHER

PHES (portosystemic hepatic encephalopathy score) and ICT (inhibitory control test)

TIPS

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability 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.

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of Montreal

Montreal, Quebec, H2X 1P1, Canada

Location

University Hospitals of Geneva

Geneva, Switzerland

Location

Related Publications (7)

  • 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.

    PMID: 20581246BACKGROUND

  • 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.

    PMID: 20820037BACKGROUND

  • 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.

    PMID: 12445419BACKGROUND

  • 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.

    PMID: 22151412BACKGROUND

  • 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.

    PMID: 21461913BACKGROUND

  • 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.

    PMID: 17222319BACKGROUND

  • 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.

    PMID: 22740290BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, and PBMCs

MeSH Terms

Conditions

AscitesHepatic EncephalopathyFibrosisHypertension, Portal

Interventions

Psychometrics

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsLiver FailureHepatic InsufficiencyLiver DiseasesDigestive System DiseasesBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Psychological TestsBehavioral Disciplines and Activities

Study Officials

  • Andres Duarte-Rojo, MD, MSc

    University of Arkansas

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 26, 2013

First Posted

January 3, 2014

Study Start

May 1, 2013

Primary Completion

January 27, 2015

Study Completion

January 27, 2015

Last Updated

April 17, 2017

Record last verified: 2017-04

Locations

US(1)CA(1)CH(1)