Total PancreatectomyNCT03864744
Hepatic Histology and Metabolism Following Total Pancreatectomy and Pancreaticoduodenectomy
An observational study of Total Pancreatectomy and Pancreaticoduodenectomy, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Total Pancreatectomy, Pancreaticoduodenectomy, Pancreatic Diabetes
- How many people
- 33 participants
- Where
- 1 siteDenmark
- Study dates
- 30 Jan 2019to 30 Aug 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- Adult, Older adult
Study population: Subjects who undergo total pancreatectomy or pancreaticoduodenectomy at Rigshospitalet, Copenhagen.
Who may be able to join
- Subject scheduled for total pancreatectomy or pancreaticoduodenectomy
- Informed consent signed prior to any study-related procedure
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hepatic Histology and Metabolism Following Total Pancreatectomy and
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.
Read the detailed 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.
- Conditions
- Total Pancreatectomy, Pancreaticoduodenectomy, Pancreatic Diabetes, Non-Alcoholic Fatty Liver Disease, Metabolic Complication, Diabetes Mellitus
- Keywords
- liver biopsy, Lipid metabolism, Glucose metabolism, Postoperative complications, Pancreatic surgery
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Postoperative Complications
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in hepatic lipid content (steatosis) after total pancreatektomy or pancreaticoduodenectomy
Evaluated by light microscopy of the liver biopsy
Measured: Baseline and after 12 months.
Secondary outcomes (19)
Hepatic lipid content
Evaluated by magnetic resonance spectroscopy
Measured: After 12 months
Diagnosis and grade of steatohepatitis (steatosis, ballooning and lobular inflammation)
Evaluated by light microscopy of the liver biopsy
Measured: Baseline and after 12 months.
Fibrosis stage (Kleiner classification)
Evaluated by light microscopy of the liver biopsy
Measured: Baseline and after 12 months.
NAFLD activity score (NAS)
Evaluated by light microscopy of the liver biopsy
Measured: Baseline and after 12 months.
Liver steatosis
Measured by controlled attenuation parametre (Fibroscan) in decibel per meter (dB/m)
Measured: After 12 months.
Liver stiffness
Measured by transcient elastrography (Fibroscan) in kilopascals (kPa)
Measured: After 12 months
Pancreatic endocrine dysfunction
defined by HbA1c ≥ 6.5% and/or need for diabetes therapy
Measured: After 12 months
Alpha- and beta cell function
measured by arginine stimulation test
Measured: After 12 months
Pancreatic exocrine dysfunction
defined by f-elastase < 100 μg/g
Measured: After 12 months
Blood markers of liver function
including alanine transaminase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltransferase (GGT), alkaline phosphatase, lactate dehydrogenase and bilirubin
Measured: Baseline and after 12 months
Blood markers of glucose metabolism
HbA1c
Measured: Baseline and after 12 months
Blood markers of glucose metabolism
Insulin
Measured: Baseline and after 12 months
Blood markers of glucose metabolism
C-peptide
Measured: Baseline and after 12 months
Blood markers of glucose metabolism
Glucagon
Measured: Baseline and after 12 months
Blood markers of lipid metabolism
including lipid profiling
Measured: Baseline and after 12 months
Blood markers of protein metabolism
including fractionated amino acids
Measured: Baseline and after 12 months
Blood markers of nutritional status
including vitamin E and D, trace elements, lymphocytes and albumin
Measured: Baseline and after 12 months
Blood markers related to bile-acid metabolism
including complement 4 (C4) and fibroblast growth factor 19 (FGF-19)
Measured: Baseline and after 12 months
Changes in NAFLD/NASH biomarkers
including FGF-21
Measured: Baseline and after 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2019
- Study start30 Jan 2019
- Primary completion30 Aug 2022 (estimated)
- Study completion30 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Total PancreatectomyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, University of Copenhagen, Herlev and Gentofte Hospital
- Responsible party
- Sponsor
- Investigators
- Filip Krag Knop, Professor, Study director, Steno Diabetes Center Copenhagen, Clinical metabolic physiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03864744
- Sponsor's protocol ID
- H-18010755
- Status last verified
- Sep 2021
- First submitted
- 1 Mar 2019
- Last updated
- 4 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatic Histology and Metabolism Following Total Pancreatectomy and
- ClinicalTrials.gov ID
- NCT03864744
- Acronym / sponsor ID
- H-18010755
- Conditions
- Total Pancreatectomy, Pancreaticoduodenectomy, Pancreatic Diabetes, Non-Alcoholic Fatty Liver Disease, Metabolic Complication, Diabetes Mellitus
- Keywords
- liver biopsy, Lipid metabolism, Glucose metabolism, Postoperative complications, Pancreatic surgery
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, University of Copenhagen, Herlev and Gentofte Hospital
- Study start
- 30 Jan 2019 (actual)
- Primary completion
- 30 Aug 2022 (estimated)
- Study completion
- 30 Aug 2022 (estimated)
- First posted
- 6 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Subjects who undergo total pancreatectomy or pancreaticoduodenectomy at Rigshospitalet, Copenhagen.
Key inclusion criteria (2 listed)
- Subject scheduled for total pancreatectomy or pancreaticoduodenectomy
- Informed consent signed prior to any study-related procedure
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in hepatic lipid content (steatosis) after total pancreatektomy or pancreaticoduodenectomy
Time frame: Baseline and after 12 months.
Evaluated by light microscopy of the liver biopsy
19 secondary outcomes
Hepatic lipid content
Time frame: After 12 months
Diagnosis and grade of steatohepatitis (steatosis, ballooning and lobular inflammation)
Time frame: Baseline and after 12 months.
Fibrosis stage (Kleiner classification)
Time frame: Baseline and after 12 months.
NAFLD activity score (NAS)
Time frame: Baseline and after 12 months.
Liver steatosis
Time frame: After 12 months.
Liver stiffness
Time frame: After 12 months
Pancreatic endocrine dysfunction
Time frame: After 12 months
Alpha- and beta cell function
Time frame: After 12 months
Pancreatic exocrine dysfunction
Time frame: After 12 months
Blood markers of liver function
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
Time frame: Baseline and after 12 months
Blood markers of lipid metabolism
Time frame: Baseline and after 12 months
Blood markers of protein metabolism
Time frame: Baseline and after 12 months
Blood markers of nutritional status
Time frame: Baseline and after 12 months
Blood markers related to bile-acid metabolism
Time frame: Baseline and after 12 months
Changes in NAFLD/NASH biomarkers
Time frame: Baseline and after 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Filip Krag Knop, Professor study director
Steno Diabetes Center Copenhagen, Clinical metabolic physiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Total Pancreatectomy and Pancreaticoduodenectomy, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in hepatic lipid content (steatosis) after total pancreatektomy or pancreaticoduodenectomy (time frame: Baseline and after 12 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2021.