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

Primary Purpose

Liver Cirrhosis, Hepatic Encephalopathy

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Lactulose and rifaximin
Branched Chain amino acids
Placebo
Sponsored by
Mette Munk Lauridsen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Liver Cirrhosis focused on measuring quality of life

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Hospital of South West Jutland
  • Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Anti cHE treatment arm

Placebo arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
January 7, 2013
Last Updated
February 22, 2016
Sponsor
Mette Munk Lauridsen
Collaborators
Region of Southern Denmark, Odense University Hospital, Hospital of South West Jutland
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1. Study Identification

Unique Protocol Identification Number
NCT01773538
Brief Title
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

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Mette Munk Lauridsen
Collaborators
Region of Southern Denmark, Odense University Hospital, Hospital of South West Jutland

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis, Hepatic Encephalopathy
Keywords
quality of life

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
136 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anti cHE treatment arm
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo arm
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lactulose and rifaximin
Intervention Description
3 months treatment. lactulose 25 Ml x3 per day. Rifaximin (550 mg) x 2 per day.
Intervention Type
Dietary Supplement
Intervention Name(s)
Branched Chain amino acids
Intervention Description
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
Other
Intervention Name(s)
Placebo
Intervention Description
Patients in the placebo-arm receives both placebo-Bramino, placebo-lactulose and placebo-rifaximin.
Primary Outcome Measure Information:
Title
Change in Continuous Reaction Time Method versus Portosystemic Encephalopathy Test
Description
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 Outcome Measure Information:
Title
Change in Continuous Reaction Time Method versus Quality of Life (QoL)
Description
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
Title
Correlation between CRT test and PSE test at inclusion
Description
The investigators wish to evaluate the correlation between the CRT and the PSE test at base line.
Time Frame
at baseline
Title
Correlation between psychometric test results and quality of life af base line
Description
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
Other Pre-specified Outcome Measures:
Title
Danish normal values for the PSE test
Description
100 normal Danish persons will be tested using the PSE test to establish the Danish norm.
Time Frame
at base line

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ove Schaffalitzky de Muckadell, Professor
Organizational Affiliation
Odense University Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jeppe Gram, PhD, MD
Organizational Affiliation
Hospital of South West Jutland
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Hendrik Vilstrup, Professor
Organizational Affiliation
Aarhus University Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital of South West Jutland
City
Esbjerg
ZIP/Postal Code
6700
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark

12. IPD Sharing Statement

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

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