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

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01773538
• Other study ID #: CHECRT
• Status: Completed
• Phase: N/A
• First received: January 7, 2013
• Last updated: February 22, 2016
• Start date: January 2013
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: Hospital of South West Jutland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research EthicsDenmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: November 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy
• Liver Cirrhosis

Intervention

Drug:
• Lactulose and rifaximin
3 months treatment. lactulose 25 Ml x3 per day. Rifaximin (550 mg) x 2 per day.

Dietary Supplement:
• Branched Chain amino acids
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.

Other:
• Placebo
Patients in the placebo-arm receives both placebo-Bramino, placebo-lactulose and placebo-rifaximin.

Locations

Country	Name	City	State
Denmark	Hospital of South West Jutland	Esbjerg
Denmark	Odense University Hospital	Odense

Sponsors (4)

Lead Sponsor	Collaborator
Mette Munk Lauridsen	Hospital of South West Jutland, Odense University Hospital, Region of Southern Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Danish normal values for the PSE test	100 normal Danish persons will be tested using the PSE test to establish the Danish norm.	at base line	No
Primary	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.	baseline and 3 months	No
Secondary	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.	baseline and 3 months	No
Secondary	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.	at baseline	No
Secondary	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.	at base line	No