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

NCT ID: NCT01773538

Last Updated: 2016-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2015-11-30

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.

Conditions

Liver Cirrhosis; Hepatic Encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

Anti cHE treatment arm

Of 150 included patients aprox. 44 regardless of CRT and PSE test outcome will be offered to enter randomisation and 3 months follow up. Half of 44 patients will receive both lactulose, rifaximin and branched chain aminoacids (Bramino) the other half placebo.

Group Type: ACTIVE_COMPARATOR

Lactulose and rifaximin

Intervention Type: DRUG

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

Branched Chain amino acids

Intervention Type: DIETARY_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.

Placebo arm

The goal of this intervention is to investigate whether the CRT method can detect an expected treatment response after initiation of the 3 named drugs know to ameliorate HE symptoms including psychometric test results.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

Lactulose and rifaximin

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

Intervention Type: DRUG

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.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

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

Intervention Type: OTHER

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Region of Southern Denmark

OTHER

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: collaborator

Esbjerg Hospital - University Hospital of Southern Denmark

OTHER

Sponsor Role: collaborator

Mette Munk Lauridsen

OTHER

Sponsor Role: lead

Responsible Party

Mette Munk Lauridsen

MD, Phd student

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ove Schaffalitzky de Muckadell, Professor

Role: STUDY_DIRECTOR

Odense University Hospital

Jeppe Gram, PhD, MD

Role: STUDY_CHAIR

Esbjerg Hospital - University Hospital of Southern Denmark

Hendrik Vilstrup, Professor

Role: STUDY_CHAIR

Aarhus University Hospital

Locations

Hospital of South West Jutland

Esbjerg, , Denmark

Odense University Hospital

Odense, , Denmark

Countries

Denmark

Other Identifiers

CHECRT

Identifier Type: -

Identifier Source: org_study_id