Diabetes After Total PancreatectomyPX-GRANCT02944110
Delineation of the Diabetogenic Role of Extrapancreatic Glucagon in Totally Pancreatectomised Patients Using Glucagon Receptor Antagonism
A study testing Glucagon receptor antagonist LY2409021 in people with Diabetes After Total Pancreatectomy, run by University Hospital, Gentofte, Copenhagen.
Trial summary
Patients with diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma levels of the 29-amino acid peptide hormone glucagon, which hitherto has been considered a pancreas-derived hormone (produced in and secreted from alpha cells in the islets of Langerhans). Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes After Total Pancreatectomy
- What is being tested?
- Glucagon receptor antagonist LY2409021
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Apr 2016to Jul 2021
- Phase
- Interventional
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Pancreatectomised patients
- Caucasian above 18 years of age who have undergone total pancreatectomy
- Normal haemoglobin
- Informed consent
- Healthy subjects
- Normal fasting plasma glucose and normal HbA1C (according to the World Health Organization (WHO) criteria)
Show all 9Show fewer
- Normal haemoglobin
- Age above 18 years
- Informed consent
Who cannot join
- Pancreatectomised patients
- Inflammatory bowel disease
- Operation within the last 3 months
- Ongoing chemotherapy or chemotherapy within the last 3 months
- Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
- Nephropathy (serum creatinine >150 µmol/l and/or albuminuria)
Show all 20Show fewer
- Severe liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3× normal values)
- Pregnancy and/or breastfeeding
- Age above 80 years
- Uncontrolled hypertension and/or significant cardiovascular disease
- Any condition that the investigator feels would interfere with trial participation
- Healthy subjects
- Diabetes or prediabetes (according to the WHO criteria)
- First-degree relatives with diabetes
- Inflammatory bowel disease
- Gastrointestinal resection and/or ostomy
- Nephropathy (serum creatinine >150 µM and/or albuminuria
- Liver disease (ALAT and/or serum ASAT >2×normal values)
- Pregnancy and/or breastfeeding
- Age above 80 years
About this study
Patients with diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma levels of the 29-amino acid peptide hormone glucagon, which hitherto has been considered a pancreas-derived hormone (produced in and secreted from alpha cells in the islets of Langerhans). In patients with diabetes, circulating glucagon concentrations are elevated in the fasting state and fail to decrease appropriately or even increase in response to an oral glucose tolerance test (OGTT) or after ingestion of a mixed meal. Hyperglucagonaemia is known to be a potent stimulator of hepatic glucose output, and, thus, contributes significantly to the fasting and postprandial hyperglycaemia characterising patients with diabetes. Despite intense research over the years the mechanisms behind the elevated glucagon levels in diabetes is still not clear. Recently, the investigators showed that totally pancreatectomised patients also show a hyperglucagonaemic response during OGTT, a finding that suggests that the pancreas is not the only source of glucagon production in man.
In the present project, the investigators wish to evaluate the impact of gastrointestinally derived glucagon secretion observed in totally pancreatectomised patients on postprandial glucose tolerance.
Read more
The investigators hypothesise that antagonisation of glucagon signalling (from gastrointestinally derived glucagon) in totally pancreatectomised patients will improve or perhaps normalise the patients glucose tolerance during a 75g-OGTT. In order to test this hypothesis, the investigators wish to apply the potent and selective oral antagonist of the human glucagon receptor LY2409021 and placebo, respectively.
The study is a randomised, placebo-controlled, double-blinded, cross-over study.
10 healthy persons and 10 pancreatectomized patients (i.e. patients who have had their pancreata removed due to pancreatic cancer or severe chronic pancreatitis) will be subjected to two experimental days with LY2409021 and placebo, respectively, on which they will undergo an OGTT followed by a fasting period and finished off with an ad libitum meal.
- Conditions
- Diabetes After Total Pancreatectomy
- Being tested
- Glucagon receptor antagonist LY2409021, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucagon receptor antagonist LY2409021Drug
single oral dose of 300mg
PlaceboDrug
Oral dose of placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| Pancreatectomised + LY2409021 | Active comparator | During the experimental day the patient will undergo a 75gr-OGTT. On the evening before the experimental day, the patient will ingest a dose of 300mg of LY2409021. Receives: Drug: Glucagon receptor antagonist LY2409021 |
| Pancreatectomised + placebo | Placebo comparator | During the experimental day the patient will undergo a 75gr-OGTT. On the evening before the experimental day, the patient will ingest placebo tablets. Receives: Drug: Placebo |
| Healthy + LLY2409021 | Active comparator | During the experimental day the subject will undergo a 75gr-OGTT. On the evening before the experimental day, the subject will ingest a dose of 300mg of LY2409021. Receives: Drug: Glucagon receptor antagonist LY2409021 |
| Healthy + placebo | Placebo comparator | During the experimental day the subject will undergo a 75gr-OGTT. On the evening before the experimental day, the subject will ingest placebo tablets. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PPG excursions measured as incremental area under curve (iAUC)
Measured: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Secondary outcomes (10)
differences in gastric emptying, measurement of s-paracetamol
measurement of time to peak and incremental area under the curve (iAUC)
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
food intake and appetite
assessed by a visual analogue scale
Measured: at time 0,30,60,90,120,150,180 minutes
resting energy expenditure (REE)
measured by calorimetry
Measured: -90,30,150 minutes
p-glucose mmol/L
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
glucagon pmol/l
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
free fatty acids μmol/l
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
p-triglyceride mmol/l
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Amino Acid concentration μmol/l
total and fractionated
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
cholecystokinin pmol/l
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Gastric inhibitory peptide (GIP) and Glucagon like peptide-1 (GLP-1) pmol/l
Measured: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2016 (estimated)
- Study startApr 2016
- Primary completionNov 2019
- Study completionJul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes After 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Filip Krag Knop, University Hospital, Gentofte, Copenhagen
- Investigators
- Filip K Knop, Professor, Principal investigator, Head of department at Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02944110
- Sponsor's protocol ID
- H-15009763
- Acronym
- PX-GRA
- Status last verified
- May 2021
- First submitted
- 24 Oct 2016
- Last updated
- 5 May 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Juel CT, Lund AB, Haedersdal S, Andersen MM, Hansen CP, Storkholm JH, van Hall G, Hartmann B, Rosenkilde MM, Kibsgaard CJ, Dela F, Albrechtsen NJW, Holst JJ, Vilsboll T, Knop FK. Using glucagon receptor antagonism to evaluate the physiological effects of extrapancreatic glucagon in totally pancreatectomised individuals: a randomised controlled trial. Diabetologia. 2025 Dec;68(12):2807-2822. doi: 10.1007/s00125-025-06534-z. Epub 2025 Sep 18.
PubMed 40968190Juel CTB, Dejgaard TF, Hansen CP, Storkholm JH, Vilsboll T, Lund A, Knop FK. Glycemic Control and Variability of Diabetes Secondary to Total Pancreatectomy Assessed by Continuous Glucose Monitoring. J Clin Endocrinol Metab. 2021 Jan 1;106(1):168-173. doi: 10.1210/clinem/dgaa731.
PubMed 33053154
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delineation of the Diabetogenic Role of Extrapancreatic Glucagon in Totally Pancreatectomised Patients Using Glucagon Receptor Antagonism
- ClinicalTrials.gov ID
- NCT02944110
- Acronym / sponsor ID
- PX-GRA / H-15009763
- Conditions
- Diabetes After Total Pancreatectomy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- Apr 2016 (actual)
- Primary completion
- Nov 2019 (actual)
- Study completion
- Jul 2021 (estimated)
- First posted
- 25 Oct 2016 (estimated)
- 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.
Patients with diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma levels of the 29-amino acid peptide hormone glucagon, which hitherto has been considered a pancreas-derived hormone (produced in and secreted from alpha cells in the islets of Langerhans). In patients with diabetes, circulating glucagon concentrations are elevated in the fasting state and fail to decrease appropriately or even increase in response to an oral glucose tolerance test (OGTT) or after ingestion of a mixed meal. Hyperglucagonaemia is known to be a potent stimulator of hepatic glucose output, and, thus, contributes significantly to the fasting and postprandial hyperglycaemia characterising patients with diabetes. Despite intense research over the years the mechanisms behind the elevated glucagon levels in diabetes is still not clear. Recently, the investigators showed that totally pancreatectomised patients also show a hyperglucagonaemic response during OGTT, a finding that suggests that the pancreas is not the only source of glucagon production in man.
In the present project, the investigators wish to evaluate the impact of gastrointestinally derived glucagon secretion observed in totally pancreatectomised patients on postprandial glucose tolerance.
The investigators hypothesise that antagonisation of glucagon signalling (from gastrointestinally derived glucagon) in totally pancreatectomised patients will improve or perhaps normalise the patients glucose tolerance during a 75g-OGTT. In order to test this hypothesis, the investigators wish to apply the potent and selective oral antagonist of the human glucagon receptor LY2409021 and placebo, respectively.
The study is a randomised, placebo-controlled, double-blinded, cross-over study.
10 healthy persons and 10 pancreatectomized patients (i.e. patients who have had their pancreata removed due to pancreatic cancer or severe chronic pancreatitis) will be subjected to two experimental days with LY2409021 and placebo, respectively, on which they will undergo an OGTT followed by a fasting period and finished off with an ad libitum meal.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pancreatectomised + LY2409021 | Active comparator | Drug: Glucagon receptor antagonist LY2409021During the experimental day the patient will undergo a 75gr-OGTT. On the evening before the experimental day, the patient will ingest a dose of 300mg of LY2409021. |
| Pancreatectomised + placebo | Placebo comparator | Drug: PlaceboDuring the experimental day the patient will undergo a 75gr-OGTT. On the evening before the experimental day, the patient will ingest placebo tablets. |
| Healthy + LLY2409021 | Active comparator | Drug: Glucagon receptor antagonist LY2409021During the experimental day the subject will undergo a 75gr-OGTT. On the evening before the experimental day, the subject will ingest a dose of 300mg of LY2409021. |
| Healthy + placebo | Placebo comparator | Drug: PlaceboDuring the experimental day the subject will undergo a 75gr-OGTT. On the evening before the experimental day, the subject will ingest placebo tablets. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Pancreatectomised patients
- Caucasian above 18 years of age who have undergone total pancreatectomy
- Normal haemoglobin
- Informed consent
- Healthy subjects
Key exclusion criteria (20 listed)
- Pancreatectomised patients
- Inflammatory bowel disease
- Operation within the last 3 months
- Ongoing chemotherapy or chemotherapy within the last 3 months
- Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glucagon receptor antagonist LY2409021single oral dose of 300mg | Drug | Healthy + LLY2409021, Pancreatectomised + LY2409021 |
| PlaceboOral dose of placebo tablets | Drug | Healthy + placebo, Pancreatectomised + placebo |
Primary outcome
PPG excursions measured as incremental area under curve (iAUC)
Time frame: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
10 secondary outcomes
differences in gastric emptying, measurement of s-paracetamol
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
food intake and appetite
Time frame: at time 0,30,60,90,120,150,180 minutes
resting energy expenditure (REE)
Time frame: -90,30,150 minutes
p-glucose mmol/L
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
glucagon pmol/l
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
free fatty acids μmol/l
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
p-triglyceride mmol/l
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Amino Acid concentration μmol/l
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
cholecystokinin pmol/l
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Gastric inhibitory peptide (GIP) and Glucagon like peptide-1 (GLP-1) pmol/l
Time frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2021.
- Derived from this study: PubMed 40968190Juel CT, Lund AB, Haedersdal S, Andersen MM, Hansen CP, Storkholm JH, van Hall G, Hartmann B, Rosenkilde MM, Kibsgaard CJ, Dela F, Albrechtsen NJW, Holst JJ, Vilsboll T, Knop FK. Using glucagon receptor antagonism to evaluate the physiological effects of extrapancreatic glucagon in totally pancreatectomised individuals: a randomised controlled trial. Diabetologia. 2025 Dec;68(12):2807-2822. doi: 10.1007/s00125-025-06534-z. Epub 2025 Sep 18.
- Derived from this study: PubMed 33053154Juel CTB, Dejgaard TF, Hansen CP, Storkholm JH, Vilsboll T, Lund A, Knop FK. Glycemic Control and Variability of Diabetes Secondary to Total Pancreatectomy Assessed by Continuous Glucose Monitoring. J Clin Endocrinol Metab. 2021 Jan 1;106(1):168-173. doi: 10.1210/clinem/dgaa731.
- Individual participant dataSharing planned: No
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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 K Knop, Professor principal investigator
Head of department at Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark
Questions about this trial
What is this clinical trial studying?
A study testing Glucagon receptor antagonist LY2409021 in people with Diabetes After Total Pancreatectomy, run by University Hospital, Gentofte, Copenhagen.
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 9 inclusion and 20 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 5 May 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
PPG excursions measured as incremental area under curve (iAUC) (time frame: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02944110, which also lists 2 linked publications.
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 5 May 2021.