Separate and Combined Extrapancreatic Effects of the Incretin Hormones (GA-19)
Primary Purpose
Pancreatectomy; Hyperglycemia
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Sponsored by
About this trial
This is an interventional basic science trial for Pancreatectomy; Hyperglycemia
Eligibility Criteria
Inclusion Criteria:
- Total pancreatectomy
- Caucasians
- Blood haemoglobin >7 mmol/l for males and >6.5 mmol/l for females
Exclusion Criteria:
- Pancreatectomy within the last 3 months
- Ongoing chemotherapy or chemotherapy within the last 3 months
- Treatment with GLP-1R agonists within the last 3 months
- Renal impairment (estimated by eGFR <60 ml/min/1.73 m2) and/or albuminuria
- Calcium related disease, hypo-/hyperthyroidism
- Known significant liver disease, ALT or AST >3 times normal value or INR outside normal range
- Severe arteriosclerotic heart disease or heart failure (NYHA group III or IV)
- Pregnancy and/or breastfeeding
- Use of more than 14 units of alcohol per week or abuse of narcotics
- Any condition that the investigator feels would interfere with trial participation
Sites / Locations
- Center for Clinical Metabolic Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
GIPRA
GLP-1RA
GIPRA + GLP-1RA
Saline
Arm Description
Outcomes
Primary Outcome Measures
Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days
mmol/l
Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days
pmol/l
Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days
pmol/l
Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days.
mmol/l lipoproteins, neutral and complex lipids.
Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days.
mg/dl
Changes in brown adipose tissue activity between interventions, assessed by thermographic camera
Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days.
μg/mL
Changes in CTX between interventions assessed through frequently blood sampling during the experimental days
ng/ml
Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days
ng/ml
Secondary Outcome Measures
Full Information
NCT ID
NCT05177653
First Posted
November 16, 2021
Last Updated
March 28, 2023
Sponsor
University Hospital, Gentofte, Copenhagen
1. Study Identification
Unique Protocol Identification Number
NCT05177653
Brief Title
Separate and Combined Extrapancreatic Effects of the Incretin Hormones
Acronym
GA-19
Official Title
Separate and Combined Extrapancreatic Effects of Glucose-dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
April 7, 2022 (Actual)
Primary Completion Date
March 3, 2023 (Actual)
Study Completion Date
March 3, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Gentofte, Copenhagen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The two gut-derived hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) is secreted from intestinal cells in relation to a meal and increase insulin secretion from the pancreas. The hormones also exert effects outside the pancreas, but especially for GIP, these are poorly investigated. Because of this, only GLP-1 based drugs (GLP-1 receptor agonists) are on the market for the treatment of type 2 diabetes and obesity. Nonetheless, a new drug is in clinical development: a combined GIP-GLP-1-receptor agonist (tirzepatide), which has shown better results than GLP-1 alone. The mechanism behind these impressive effects are unknown and in this study, the investigators will look into the exptrapancreatic effects of GIP and GLP-1, separate and combined and thus elucidate the mechanisms of action of this new drug class.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatectomy; Hyperglycemia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GIPRA
Arm Type
Experimental
Arm Title
GLP-1RA
Arm Type
Experimental
Arm Title
GIPRA + GLP-1RA
Arm Type
Experimental
Arm Title
Saline
Arm Type
Placebo Comparator
Intervention Type
Other
Intervention Name(s)
Intravenous infusion
Intervention Description
GIP receptor antagonist (GIP(3-30)NH2)
Intervention Type
Other
Intervention Name(s)
Intravenous infusion
Intervention Description
GLP-1 receptor antagonist (exendin(9-39)NH2)
Intervention Type
Other
Intervention Name(s)
Intravenous infusion
Intervention Description
GIP(3-30)NH2 and exendin(9-39)NH2
Intervention Type
Other
Intervention Name(s)
Intravenous infusion
Intervention Description
Saline
Primary Outcome Measure Information:
Title
Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days
Description
mmol/l
Time Frame
Up to two months
Title
Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days
Description
pmol/l
Time Frame
Up to two months
Title
Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days
Description
pmol/l
Time Frame
Up to two months
Title
Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days.
Description
mmol/l lipoproteins, neutral and complex lipids.
Time Frame
Up to two months
Title
Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days.
Description
mg/dl
Time Frame
Up to two months
Title
Changes in brown adipose tissue activity between interventions, assessed by thermographic camera
Time Frame
Up to two months
Title
Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days.
Description
μg/mL
Time Frame
Up to two months
Title
Changes in CTX between interventions assessed through frequently blood sampling during the experimental days
Description
ng/ml
Time Frame
Up to two months
Title
Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days
Description
ng/ml
Time Frame
Up to two months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Total pancreatectomy
Caucasians
Blood haemoglobin >7 mmol/l for males and >6.5 mmol/l for females
Exclusion Criteria:
Pancreatectomy within the last 3 months
Ongoing chemotherapy or chemotherapy within the last 3 months
Treatment with GLP-1R agonists within the last 3 months
Renal impairment (estimated by eGFR <60 ml/min/1.73 m2) and/or albuminuria
Calcium related disease, hypo-/hyperthyroidism
Known significant liver disease, ALT or AST >3 times normal value or INR outside normal range
Severe arteriosclerotic heart disease or heart failure (NYHA group III or IV)
Pregnancy and/or breastfeeding
Use of more than 14 units of alcohol per week or abuse of narcotics
Any condition that the investigator feels would interfere with trial participation
Facility Information:
Facility Name
Center for Clinical Metabolic Research
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Separate and Combined Extrapancreatic Effects of the Incretin Hormones
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