- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT03260036
Hepatic Urea Nitrogen Handling in Patients With NASH
The Effect of Bariatric Surgery on Hepatic Urea Nitrogen Handling and Cognitive Functions in Patients With Severe Non-alcoholic Fatty Liver Disease
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Forventet)
Kontakter og lokationer
Studiesteder
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Aarhus, Danmark, 8000
- Rekruttering
- Department of Hepatology and Gastroenterology, Aarhus University Hospital
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Kontakt:
- Karen Louise Thomsen, MD, PhD
- Telefonnummer: +45 78463892
- E-mail: karethom@rm.dk
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Changes in Functional Hepatic Nitrogen Clearance (FHNC)
Tidsramme: Baseline and 18 months
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FHNC is a validated method for assessing the conversion of amino-nitrogen to urea-nitrogen by the liver
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Baseline and 18 months
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Urea cycle enzymes (protein and gene level)
Tidsramme: Baseline and 18 months
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Examined in liver biopsy
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Baseline and 18 months
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Changes in The Portosystemic Encephalopathy Syndrome-Test
Tidsramme: Baseline and 18 months
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To evaluate changes in the patient's cognitive functions
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Baseline and 18 months
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Changes in Continuous Reaction Time Test
Tidsramme: Baseline and 18 months
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To evaluate changes in the patient's cognitive functions
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Baseline and 18 months
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Changes in Critical Flicker Frequency
Tidsramme: Baseline and 18 months
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To evaluate changes in the patient's cognitive functions
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Baseline and 18 months
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Changes in EEG
Tidsramme: Baseline and 18 months
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To evaluate potential changes in the patient's EEG
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Baseline and 18 months
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Karen Louise Thomsen, MD, PhD, Aarhus University Hospital
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Forventet)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- FHNC-bariatric
Plan for individuelle deltagerdata (IPD)
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