Diagnosing Minimal Hepatic Encephalopathy

• Conditions: Hepatic Encephalopathy; Liver Cirrhosis
• Interventions: Diagnostic Test: Simultaneous EEG and CRT

• Registration Number: NCT05433948
• Lead Sponsor: Esbjerg Hospital - University Hospital of Southern Denmark

Brief Summary

Our purpose is to

1. Examine the correlation between MDF in a resting EEG, recorded just before the CRT test, and the variance in reaction times indicated by the CRT index

2. At simultaneous CRT and EEG recording, examine whether a change in EEG is seen immediately before an extended reaction time occurs (defined by the 75th percentile). This will shed light on a direct pathophysiological association between what is measured with EEG and CRT.

3. Investigate whether cyclicity can be detected in the continuous reaction times and if so, whether amplitude and wavelength in this cyclic activity are correlated to EEG parameters.

4. Examine whether a response to standard HE treatment can be detected with EEG in patients who are thought to suffer from it. As well as if baseline outcome predict future hepatic encephalopathy.

5. With a view to further validating our findings, investigators want to correlate results from EEG and CRT with the most internationally widespread psychometric test, the Portosystemic Encephalopathy test (PSE), which necessitates the establishment of Danish normal values. A secondary purpose of this study is therefore

6. To establish Danish normal values for the PSE test and the Animal Naming test in Danes

Detailed Description

Not available

Study Timeline

• Study Start: 2019-12-01
• Study First Submitted: 2022-06-12
• Study First Submitted QC: 2022-06-22
• Study First Posted: 2022-06-27
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-12-02
• Primary Completion: 2026-12-01
• Study Completion: 2031-12-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

Not provided

Exclusion Criteria

1. Organic brain disease (eg previous epilepsy, apoplexy, dementia)
2. Hyponatraemia (Na <124 mmol / L)
3. Sepsis one week prior to tests.
4. Heart failure (EC less than 30% or NYHA class III and IV)
5. Severe chronic obstructive pulmonary disease (GOLD stage 3 and 4 ie FEV1 / FVC below 0.7 and FEV1 <50% of expected value)
6. Highly controllable diabetes (HbA1C> 60 mmol / mol)
7. Renal failure (eGFR below 60)
8. Known neurological diseases (epilepsy, stroke, dementia)
9. Intake of coffee or alcohol 6 hours before tests and change of dose in psychoactive drugs within 6 days of the test (morphine, antipsychotics, antidepressants) -

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Liver cirrhosis with normal cognition	Simultaneous EEG and CRT	Liver cirrhosis and performs normally in all psychometric tests. n=100
Liver cirrhosis with minimal hepatic encephalopathy	Simultaneous EEG and CRT	Liver cirrhosis and performs abnormally en 2 or more psychometric test. n=100
Liver cirrhosis and overt hepatic encephalopathy	Simultaneous EEG and CRT	West Haven grade 2 or more. n=50
Healthy control persons	Simultaneous EEG and CRT	Completely healthy persons, age, and gender-matched to cirrhosis patients. n=100

Primary Outcome Measures

Name	Time	Method
Change in EEG spectral and frequency analysis with a clinically indicated standard treatment for minimal hepatic encephalopathy	Up to 60 months	Some patients will be found eligible for treatment with lactulose or rifaximin due to signs of minimal hepatic encephalopathy. Investigators will use EEG relative theta and delta activity to measure the efficacy of the treatment.
Concordant changes in reaction times and in EEG spectral and frequency analysis	Up to 60 months	During CRT 150 reaction times are measured. Investigators want to measure if prolonged reaction times \>75 percentile are preceded by spectral and frequency changes in EEG. For EEG investigators will assess relative theta and delta activity. EEG and CRT will be done simultaneously.
Observation of cyclic activity in continous reaction times (CRT measures)	Up to 60 months	Apply mathematically modeled time analysis to establish cyclicity in the 150 measures reaction times and examine if cyclic activity correlates to relative theta and delta activity in the EEG.

Trial Locations

Locations (1)

Hospital of South West Jutland; 🇩🇰 Esbjerg, Denmark