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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hospital of South West Jutland
Sponsor:
Collaborators:
Region Southern Denmark
Odense University Hospital
Hospital of South West Jutland
Information provided by (Responsible Party):
Mette Munk Lauridsen, Hospital of South West Jutland
ClinicalTrials.gov Identifier:
NCT01773538
First received: January 7, 2013
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention
Liver Cirrhosis
Hepatic Encephalopathy
Drug: Lactulose and rifaximin
Dietary Supplement: Branched Chain amino acids
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
Official Title: Diagnosis of Covert/Minimal Hepatic Encephalopathy by Means of Continuous Reaction Time Measurement

Resource links provided by NLM:


Further study details as provided by Hospital of South West Jutland:

Primary Outcome Measures:
  • Change in Continuous Reaction Time Method versus Portosystemic Encephalopathy Test [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
    The investigators are evaluating if the CRT and PSE test are in accordance at inclusion and after 3 months of treatment.


Secondary Outcome Measures:
  • Change in Continuous Reaction Time Method versus Quality of Life (QoL) [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
    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.

  • Correlation between CRT test and PSE test at inclusion [ Time Frame: at baseline ] [ Designated as safety issue: No ]
    The investigators wish to evaluate the correlation between the CRT and the PSE test at base line.

  • Correlation between psychometric test results and quality of life af base line [ Time Frame: at base line ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Danish normal values for the PSE test [ Time Frame: at base line ] [ Designated as safety issue: No ]
    100 normal Danish persons will be tested using the PSE test to establish the Danish norm.


Estimated Enrollment: 250
Study Start Date: January 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
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.
Placebo Comparator: 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.
Other: Placebo
Patients in the placebo-arm receives both placebo-Bramino, placebo-lactulose and placebo-rifaximin.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773538

Contacts
Contact: Mette Munk Lauridsen, MD +4561661192 mettelauridsen@gmail.com
Contact: Ove Schaffalitzky, Professor sdm@ouh.regionsyddanmark.dk

Locations
Denmark
Hospital of South West Jutland Recruiting
Esbjerg, Denmark, 6700
Contact: Mette Munk Lauridsen, MD         
Principal Investigator: Mette Munk Lauridsen, MD         
Odense University Hospital Recruiting
Odense, Denmark, 5000
Contact: Ove Scahffalitzky de Muckadell, Professor       sdm@ouh.regionsyddanmark.dk   
Sub-Investigator: Ove Schaffalitzkt de Muckadell, Professor         
Sponsors and Collaborators
Mette Munk Lauridsen
Region Southern Denmark
Odense University Hospital
Hospital of South West Jutland
Investigators
Study Director: Ove Schaffalitzky de Muckadell, Professor Odense University Hospital
Study Chair: Jeppe Gram, PhD, MD Hospital of South West Jutland
Study Chair: Hendrik Vilstrup, Professor Aarhus University Hospital
  More Information

No publications provided

Responsible Party: Mette Munk Lauridsen, MD, Phd student, Hospital of South West Jutland
ClinicalTrials.gov Identifier: NCT01773538     History of Changes
Other Study ID Numbers: CHECRT
Study First Received: January 7, 2013
Last Updated: August 22, 2014
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency

Keywords provided by Hospital of South West Jutland:
quality of life

Additional relevant MeSH terms:
Brain Diseases
Liver Cirrhosis
Hepatic Encephalopathy
Central Nervous System Diseases
Nervous System Diseases
Liver Diseases
Digestive System Diseases
Liver Failure
Hepatic Insufficiency
Brain Diseases, Metabolic
Metabolic Diseases
Rifaximin
Lactulose
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 16, 2014