Diagnosis of Covert/Minimal Hepatic Encephalopathy by Means of Continuous Reaction Time Measurement

Mette Munk Lauridsen136 enrolled

Overview

The investigators wish to investigate how the Continuous Reaction Time (CRT) method can be used in the diagnosis and monitoring of covert hepatic encephalopathy (cHE)in patients with cirrhosis of the liver. The hypothesis is that the CRT method (duration 10-2 minutes) can serve as a tool in the diagnosis and monitoring of cHE and is an alternative to using the Portosystemic Encephalopathy Test (PSE)(duration 20-25 minutes).

Objective: The aim of this project is to investigate whether continuous reaction time measurements (CRT) are suitable as a screening and monitoring tool for covert hepatic encephalopathy (c/mHE). Method: Sub-protocol 1: As a part of this PhD protocol 100 healthy individuals and 50 with chronic disease (not liver cirrhosis) will be tested using the CRT and PSE tests. This is to determine the normal range for the PSE test in the Danish population. Sub-protocol 2: A total of 120 (aprox. 145 to adjust for drop outs) patients with liver cirrhosis from two Danish hospitals will be examined with both CRT and with the test that is the closest we get to a gold standard, namely portosystemic encephalopathy test (PSE). We wish to examine if the CRT test agrees with the PSE test, which may be to time consuming to perform in everyday clinical practice, and with quality of life scores (SF-36 and Sickness Impact Profile). The relationship between the CRT and PSE test and various blood tests and the Charlston co-morbidity score will also be examined. Sub-protocol 3: Forty-four of the 120 included patients will, regardless of CRT test result, be randomized to treatment with lactulose, rifaximin and branched chain amino acids (BCAA) or placebo lactulose, rifaximin and BCAA. This is to evaluate whether the CRT method is able to detect a response to treatment, and see if changes in psychometric tests (PSE and CRT) are in accordance with quality of life scores and predicts subsequent development of overt hepatic encephalopathy. Perspective: CRT method should, if it proves good enough, continue to be the Danish test of choice and hopefully be more widely used in our country. The validation of tests for the diagnosis of covert hepatic encephalopathy will give cirrhotic patients with covert hepatic encephalopathy and reduced quality of life the best opportunity to be diagnosed and offered appropriate treatment. If the CRT method is not able to identify a population that benefits from anti-encephalopathy treatment other screening and monitoring tests should be used.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

DOUBLE

Enrollment

136

Conditions

Liver Cirrhosis Hepatic Encephalopathy

Interventions

Lactulose and rifaximinDRUG

3 months treatment. lactulose 25 Ml x3 per day. Rifaximin (550 mg) x 2 per day.

Branched Chain amino acidsDIETARY_SUPPLEMENT

30 grams of branched chain amino acids (Bramino) per day is given to the patients in the antiHE treatment arm along with lactulose and rifaximin.

PlaceboOTHER

Patients in the placebo-arm receives both placebo-Bramino, placebo-lactulose and placebo-rifaximin.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: For healthy volunteers: * Age\> 18 years * Written informed consent * Speak and understand Danish For patients: * Age \> 18 years * Liver cirrhosis confirmed by biopsy or appropriate clinic and biochemistry, and imaging. * Written informed consent * Speak and understand Danish Exclusion Criteria (patients and control persons): * Clinical manifest hepatic encephalopathy * Consumption of psychoactive substances within 6 days of test * Organic brain disease (i.e. prior stroke, dementia) * Hypothyroidism * Renal failure (creatinine\> 150 mg / dL) * Hyponatremia (Na \<125 mmol / L) * Sepsis or bleeding within one week prior to testing. * Serious sleep disorders * Current treatment with lactulose, rifaximin or BCAA

Locations (2)

Hospital of South West Jutland

Esbjerg, Denmark

Odense University Hospital

Odense, Denmark

Outcomes

Primary Outcomes

Change in Continuous Reaction Time Method versus Portosystemic Encephalopathy Test

The investigators are evaluating if the CRT and PSE test are in accordance at inclusion and after 3 months of treatment.

Time frame: baseline and 3 months

Secondary Outcomes

Change in Continuous Reaction Time Method versus Quality of Life (QoL)

The results from both CRT and PSE test will be compared to the out come of the SF-36 and the SIP (Sickness impact profile) QoL measurements.

Time frame: baseline and 3 months

Correlation between CRT test and PSE test at inclusion

The investigators wish to evaluate the correlation between the CRT and the PSE test at base line.

Time frame: at baseline

Correlation between psychometric test results and quality of life af base line

The investigators wish to evaluate the correlation between the psychometric test results (CRT test result and PSE test result) and quality of life. The scientific question is which test correlates best to QoL.

Time frame: at base line

Data from ClinicalTrials.gov

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