Hepatic Urea Nitrogen Handling in Patients With NASH

May 13, 2024 updated by: University of Aarhus

The Effect of Bariatric Surgery on Hepatic Urea Nitrogen Handling and Cognitive Functions in Patients With Severe Non-alcoholic Fatty Liver Disease

The aim of the project is to investigate the metabolic regulation of the hepatic urea nitrogen handling and various cognitive functions measured by psychometric and neurophysiological tests before and after bariatric surgery in patients with non-alcoholic fatty liver disease (NAFLD).

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

NAFLD is the most common cause of chronic liver disease in the western world affecting 10-30% of the general population. It is strongly associated with the metabolic syndrome caused by overweight and obesity. NAFLD is a spectrum of liver disease ranging from steatosis (hepatocytic fat accumulation occurs without hepatocellular injury), to non-alcoholic steatohepatitis (NASH) (steatosis is accompanied by inflammation and hepatocyte injury with or without fibrosis) and to cirrhosis in patients that are not consuming excessive alcohol. The prognosis of patients with simple steatosis appears benign whereas NASH often has a progressive course with increased liver-related morbidity and mortality.

Patients with liver disease often have impairment of metabolic liver functions. The liver has numerous functions, which are essential for maintenance of life e.g. urea synthesis. This function is central in whole body nitrogen (N) homeostasis and removes ammonia, which is produced during N conversion and is extremely toxic especially for brain functions. Impairment of urea synthesis causes increased ammonia concentrations in the blood, which is taken up by the brain and contributes to development of hepatic encephalopathy in patients with liver disease. This condition is one of the most debilitating complications of liver disease as it affects cognitive functions and with increasing severity also behaviour and motor function. The mild stage (termed minimal hepatic encephalopathy) causes subtle cognitive dysfunction, which can only be detected by means of special tests. The more severe stages (manifest hepatic encephalopathy) are accompanied by manifest dysfunction of sleep pattern and orientation eventually leading to liver coma. The condition is reversible and no structural brain damage occurs.

We seek to investigate the consequences of bariatric surgery on liver and brain function with a special focus on NASH patients. The investigations will comprise examination of the capacity for urea synthesis and various psychometric and neurophysiological tests to evaluate the patient's cognitive functions before and 18 months after surgery.

A liver biopsy will be availed at the time of surgical intervention and genetic and functional characterization of urea cycle enzymes will be performed to correlate with histological scores, clinical disease staging and ammonia/capacity for urea synthesis. A further liver biopsy will be performed after 18 months to determine if there has been any change in NAFLD disease stage and urea cycle enzymes after intervention.

Study Type

Observational

Enrollment (Estimated)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8000
        • Department of Hepatology and Gastroenterology, Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Obese patients referred for bariatric surgery

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Referred for bariatric surgery (BMI > 40 kg/m2 or BMI > 35 kg/m2 and obesity-related complications
  • Steatosis on ultrasound (US)
  • Alcohol intake < 40g/day
  • Exclusion of other liver diseases

Exclusion Criteria:

  • Chronic inflammatory diseases
  • Acute severe bacterial infection (sepsis, pneumonia, urinary tract infection etc.)
  • Cancer
  • Neurological diseases
  • Prednisolone treatment within the last 8 weeks
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Functional Hepatic Nitrogen Clearance (FHNC)
Time Frame: Baseline and 18 months
FHNC is a validated method for assessing the conversion of amino-nitrogen to urea-nitrogen by the liver
Baseline and 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urea cycle enzymes (protein and gene level)
Time Frame: Baseline and 18 months
Examined in liver biopsy
Baseline and 18 months
Changes in The Portosystemic Encephalopathy Syndrome-Test
Time Frame: Baseline and 18 months
To evaluate changes in the patient's cognitive functions
Baseline and 18 months
Changes in Continuous Reaction Time Test
Time Frame: Baseline and 18 months
To evaluate changes in the patient's cognitive functions
Baseline and 18 months
Changes in Critical Flicker Frequency
Time Frame: Baseline and 18 months
To evaluate changes in the patient's cognitive functions
Baseline and 18 months
Changes in EEG
Time Frame: Baseline and 18 months
To evaluate potential changes in the patient's EEG
Baseline and 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Principal Investigator: Karen Louise Thomsen, MD, PhD, Aarhus University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 21, 2017

Primary Completion (Estimated)

August 21, 2025

Study Completion (Estimated)

August 21, 2025

Study Registration Dates

First Submitted

August 16, 2017

First Submitted That Met QC Criteria

August 23, 2017

First Posted (Actual)

August 24, 2017

Study Record Updates

Last Update Posted (Actual)

May 14, 2024

Last Update Submitted That Met QC Criteria

May 13, 2024

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FHNC-bariatric

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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