Evaluation of Minimal Hepatic Encephalopathy in Patients With Cirrhosis and Portal Hypertension (Evencipor)

January 4, 2024 updated by: IHU Strasbourg
Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment and represents the mildest type of hepatic encephalopathy (HE). Portal hypertension is the main complication of cirrhosis and is responsible of severe complications such as HE. The consequence of portal hypertension is the formation of the spontaneous portosystemic shunts (SPSS). The relationship between the SPSS and their characteristics and the prevalence of MHE in patient with cirrhosis is poorly known. The main objective of this study is to evaluate the MHE in patients with cirrhosis and portal hypertension.

Study Overview

Detailed Description

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment and represents the mildest type of hepatic encephalopathy (HE). It is a frequent complication of the liver disease, affecting up to 80% of tested patients. MHE affects severely the lives of patients by altering their quality-of-life and their socioeconomic status and is strongly associated to the development of overt HE. Portal hypertension is the main complication of cirrhosis and is responsible of severe complications such as HE. The consequence of portal hypertension is the formation of the spontaneous portosystemic shunts (SPSS). Their presence has been associated with recurrent or persistent HE. The relationship between the SPSS and their characteristics and the prevalence of MHE in patient with cirrhosis is poorly known.

Patients with compensated cirrhosis and portal hypertension will be considered for inclusion. After written inform consent, the serum ammonia, psychometric hepatic encephalopathy score (PHES) and the animal naming test (ANT) will be performed to evaluate the presence of MHE. Patients diagnosed with MHE will be treated and a new evaluation will be performed 6 months later.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient with cirrhosis and portal hypertension older than 18 old
  • Patient who underwent a CT scan or MRI in the last 3 months
  • The Mini-Mental State (MMS) test >25.
  • Patient capable of receiving and understanding information relating to the study and of giving his written informed consent.
  • Patient affiliated to the French social security system

Exclusion Criteria:

  • Cirrhotic patient with overt HE or history of persistent or recurrent HE.
  • Hepatocellular carcinoma beyond Milan criteria.
  • Portal vein thrombosis.
  • Previous transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunt.
  • Presence of neurological or psychiatric disorder.
  • Patient with treatment by benzodiazepines or opioid substitution.
  • Pregnant or nursing women
  • Patient in exclusion period of a previous study
  • Patient under guardianship, trusteeship or the protection of justice or incapable of giving their own informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with compensated cirrhosis and portal hypertension
Assessment of MHE at the inclusion and 6 months after treatment if diagnosed with MHE: Serum ammonia analysis, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT) and evaluation of abdominal imaging, liver and splenic transient elastography, gastroscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of MHE in patients with cirrhosis and portal hypertension by serum ammonia analysis
Time Frame: Day 1
The serum ammonia analysis measures the level of ammonia in the blood, expressed in micromoles per liter. Average values in venous blood are between 11,2 and 48,2 micromoles per liter.
Day 1
Evaluation of MHE in patients with cirrhosis and portal hypertension by the psychometric hepatic encephalopathy score (PHES)
Time Frame: Day 1

The psychometric hepatic encephalopathy score (PHES) is composed of five tests, number connection test-A (NCT-A), number connection test-B (NCT-B), serial dotting test (SDT), line tracing test (LTT) and digit symbol test (DST). The results of the NCT-A, NCT-B, and SDT were measured as seconds, including the time needed to correct any errors, and the result of DST was measured as points. The results of the LTT were measured as both the time needed to complete the test (LTTt, seconds) and as the error score (LTTe), LTT = (1 + LTTe/100) × LTTt. Accordingly, a higher result of DST equals better performance, and lower results on the other tests equal better performance.

The final score of PHES is generated from the sum of the scores of five tests, which ranged between +5 and -15. The result of the PHES is expressed in number of standard deviations (SD) from a population matched on age and level of education. A threshold (- 4DS) defines the EHM according to current recommendations.

Day 1
Evaluation of MHE in patients with cirrhosis and portal hypertension by the animal naming test (ANT)
Time Frame: Day 1
The animal naming test (ANT) is an analysis of semantic fluency consisting of saying as many animal names as possible within one minute. The French recommendations developed by the French Association for The Liver Study (AFEF) suggests a limit of 20 animal names in 1 min. Below, the existence of MHE is likely.
Day 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the correlation between MHE and portal hypertension by the mean of blood test and abdominal imaging
Time Frame: 1 month
Portal hypertension will be qualitatively assessed (presence/absence) by blood tests (Plaquettes < 150 000 /mm3) and abdominal imaging (contrast-enhanced abdominal computed tomography (CT) or abdominal magnetic resonance imaging (MRI))
1 month
Evaluation of the correlation between MHE and splenic congestion by elastography
Time Frame: Day 1
Splenic congestion will be qualitatively assessed (presence/absence) by splenic elastography (≥ 52 kPa)
Day 1
Evaluation of the correlation between MHE and liver fibrosis by elastography
Time Frame: Day 1
Liver fibrosis will be qualitatively assessed (presence/absence) by liver transient elastography (fibroscan > 14 kPa)
Day 1
Evaluation of the correlation between MHE and sarcopenia by imaging
Time Frame: Day 1
Sarcopenia will be qualitatively assessed (presence/absence) by L3 Skeletal muscle index (L3 SMI) measured by CT scan: the muscle area at L3 vertebra level. The threshold values that define sarcopenia are: <50 cm² / m² for men and <39 cm² / m² for women.
Day 1
Evaluation of the correlation between MHE and myosteatosis by imaging
Time Frame: Day 1
Myosteatosis is defined by muscle attenuation on CT scan which reflects fatty infiltration muscular. The average muscle attenuation will be reported for the calculated muscle area with sectional image similar to that provided to calculate the L3 SMI. The definition of the myosteatosis is <41 Hounsfield Unit (HU) for a BMI ≤ 24.9 kg / m² and ≥ 33 HU for patients with a BMI ≥ 25 kg / m².
Day 1
Evaluation of the neurologic assessment in patients diagnosed with MHE after 6 months of treatment by serum ammonia analysis
Time Frame: Month 7
The serum ammonia analysis measures the level of ammonia in the blood, expressed in micromoles per liter. Average values in venous blood are between 14 and 38 micromoles per liter.
Month 7
Evaluation of the neurologic assessment in patients diagnosed with MHE after 6 months of treatment by the psychometric hepatic encephalopathy score (PHES)
Time Frame: Month 7

The psychometric hepatic encephalopathy score (PHES) is composed of five tests, number connection test-A (NCT-A), number connection test-B (NCT-B), serial dotting test (SDT), line tracing test (LTT) and digit symbol test (DST). The results of the NCT-A, NCT-B, and SDT were measured as seconds, including the time needed to correct any errors, and the result of DST was measured as points. The results of the LTT were measured as both the time needed to complete the test (LTTt, seconds) and as the error score (LTTe), LTT = (1 + LTTe/100) × LTTt. Accordingly, a higher result of DST equals better performance, and lower results on the other tests equal better performance.

The final score of PHES is generated from the sum of the scores of five tests, which ranged between +5 and -15. The result of the PHES is expressed in number of standard deviations (SD) from a population matched on age and level of education. A threshold (- 4DS) defines the EHM according to current recommendations.

Month 7
Evaluation of the neurologic assessment in patients diagnosed with MHE after 6 months of treatment by the animal naming test (ANT)
Time Frame: Month 7
The animal naming test (ANT) is an analysis of semantic fluency consisting of saying as many animal names as possible within one minute. The French recommendations developed by the French Association for The Liver Study (AFEF) suggests a limit of 20 animal names in 1 min. Below, the existence of MHE is likely.
Month 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Simona TRIPON, MD, PhD, Service d'Hépato-Gastroentérologie, NHC, Strasbourg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2021

Primary Completion (Estimated)

March 25, 2024

Study Completion (Estimated)

March 25, 2025

Study Registration Dates

First Submitted

March 16, 2021

First Submitted That Met QC Criteria

March 18, 2021

First Posted (Actual)

March 19, 2021

Study Record Updates

Last Update Posted (Actual)

January 5, 2024

Last Update Submitted That Met QC Criteria

January 4, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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