Clinical trial NCT01773538: Diagnosis of Covert/Minimal Hepatic Encephalopathy by Means of Continuous Reaction Time Measurement
Official title: Diagnosis of Covert/Minimal Hepatic Encephalopathy by Means of Continuous Reaction Time Measurement
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Cirrhosis
Hepatic Encephalopathy
Keywords: quality of life
Lead sponsor: Esbjerg Hospital - University Hospital of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Region of Southern Denmark
name: Odense University Hospital
name: Esbjerg Hospital - University Hospital of Southern Denmark
First posted: 2013-01-23
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Continuous Reaction Time Method versus Portosystemic Encephalopathy Test
timeFrame: baseline and 3 months
Secondary outcomes:
measure: Change in Continuous Reaction Time Method versus Quality of Life (QoL)
timeFrame: baseline and 3 months
measure: Correlation between CRT test and PSE test at inclusion
timeFrame: at baseline
measure: Correlation between psychometric test results and quality of life af base line
timeFrame: at base line
Other outcomes:
measure: Danish normal values for the PSE test
timeFrame: at base line
Locations:
city: Esbjerg
country: Denmark
facility: Hospital of South West Jutland
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Ove Schaffalitzky de Muckadell, Professor
role: STUDY_DIRECTOR
affiliation: Esbjerg Hospital - University Hospital of Southern Denmark
name: Jeppe Gram, PhD, MD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Hendrik Vilstrup, Professor
role: STUDY_CHAIR
References: