Hepatic Histology and Metabolism Following Total Pancreatectomy and Pancreaticoduodenectomy

Diabetes Mellitus Clinical Trial

Official title:

Hepatic Histology and Metabolism Following Total Pancreatectomy and

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03864744
• Other study ID #: H-18010755
• Status: Enrolling by invitation
• Start date: January 30, 2019
• Est. completion date: August 30, 2022

Study information

• Verified date: September 2021
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of the study is to investigate the development of NAFLD following total pancreatectomy and pancreaticoduodenectomy and to explore the histological and metabolic changes following the procedures.

Description:

After total pancreatectomy patients are treated with exogenous insulin and pancreatic enzyme supplementation in order to treat the endocrine and exocrine insufficiencies inherently occurring postoperatively. In addition to secondary diabetes and insufficient digestive capacity, totally pancreatectomised patients face a high risk of developing non-alcoholic hepatic steatosis. Under normal circumstances non-alcoholic fatty liver disease is regarded as the hepatic manifestation of metabolic syndrome and pathophysiologically related to excess energy intake and insulin resistance resulting in fat accumulation in adipose tissue as well as in the liver. Thus, the high incidence of hepatic steatosis following total pancreatectomy is surprising as patients typically are lean, peripherally insulin sensitive and properly insulinised.Interestingly, the pancreatic hormone glucagon has been implicated in lipid metabolism and recent human data from studies investigating the effect of glucagon receptor antagonism suggest that glucagon signalling may be essential for maintaining a fat-free liver. This makes the investigators speculate that the decreased glucagon levels following pancreatic surgery may play a hitherto unrecognised role in the development of hepatic steatosis after the operation.

The study will include 33 patients scheduled for pancreatectomy (total or pancreaticoduodenectomy). They will be followed for one year. A liver biopsy will be collected during the operation on all patients. After 12 months, participants will undergo magnetic resonance spectroscopy and those who have hepatic lipid content ≥2% will undergo an ultrasound-guided percutaneous liver biopsy. Furthermore, all participants will undergo a metabolic evaulation after one year.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 33
• Est. completion date: August 30, 2022
• Est. primary completion date: August 30, 2022
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Subject scheduled for total pancreatectomy or pancreaticoduodenectomy

• Informed consent signed prior to any study-related procedure

Exclusion Criteria:

• Known liver disease before total pancreatectomy or pancreaticoduodenectomy (excluding NAFLD)

• Severe co-morbid disease (besides from the indication for the pancreas surgery)

• Pregnancy

• Any condition that the investigator feels would interfere with the safety of the trial participation or the safety of the subject

• Metastatic disease

Percutaneous liver biopsy exclusion criteria (to be evaluated before last visit)

• MR spectroscopy demonstrating lipid content <2%

• Haemoglobin <6 mmol/L

• INR >1.5

• Trombocytes <40 × 109/L

• Skin infection in area where biopsy will be sampled

Related Conditions & MeSH terms

• Diabetes Mellitus
• Fatty Liver
• Liver Diseases
• Metabolic Complication
• Non-Alcoholic Fatty Liver Disease
• Pancreatic Diabetes
• Pancreaticoduodenectomy
• Total Pancreatectomy

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Copenhagen	Hellerup

Sponsors (4)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	Herlev and Gentofte Hospital, Rigshospitalet, Denmark, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in hepatic lipid content (steatosis) after total pancreatektomy or pancreaticoduodenectomy	Evaluated by light microscopy of the liver biopsy	Baseline and after 12 months.
Secondary	Hepatic lipid content	Evaluated by magnetic resonance spectroscopy	After 12 months
Secondary	Diagnosis and grade of steatohepatitis (steatosis, ballooning and lobular inflammation)	Evaluated by light microscopy of the liver biopsy	Baseline and after 12 months.
Secondary	Fibrosis stage (Kleiner classification)	Evaluated by light microscopy of the liver biopsy	Baseline and after 12 months.
Secondary	NAFLD activity score (NAS)	Evaluated by light microscopy of the liver biopsy	Baseline and after 12 months.
Secondary	Liver steatosis	Measured by controlled attenuation parametre (Fibroscan) in decibel per meter (dB/m)	After 12 months.
Secondary	Liver stiffness	Measured by transcient elastrography (Fibroscan) in kilopascals (kPa)	After 12 months
Secondary	Pancreatic endocrine dysfunction	defined by HbA1c = 6.5% and/or need for diabetes therapy	After 12 months
Secondary	Alpha- and beta cell function	measured by arginine stimulation test	After 12 months
Secondary	Pancreatic exocrine dysfunction	defined by f-elastase < 100 µg/g	After 12 months
Secondary	Blood markers of liver function	including alanine transaminase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltransferase (GGT), alkaline phosphatase, lactate dehydrogenase and bilirubin	Baseline and after 12 months
Secondary	Blood markers of glucose metabolism	HbA1c	Baseline and after 12 months
Secondary	Blood markers of glucose metabolism	Insulin	Baseline and after 12 months
Secondary	Blood markers of glucose metabolism	C-peptide	Baseline and after 12 months
Secondary	Blood markers of glucose metabolism	Glucagon	Baseline and after 12 months
Secondary	Blood markers of lipid metabolism	including lipid profiling	Baseline and after 12 months
Secondary	Blood markers of protein metabolism	including fractionated amino acids	Baseline and after 12 months
Secondary	Blood markers of nutritional status	including vitamin E and D, trace elements, lymphocytes and albumin	Baseline and after 12 months
Secondary	Blood markers related to bile-acid metabolism	including complement 4 (C4) and fibroblast growth factor 19 (FGF-19)	Baseline and after 12 months
Secondary	Changes in NAFLD/NASH biomarkers	including FGF-21	Baseline and after 12 months