Clinical trial NCT05177653: Separate and Combined Extrapancreatic Effects of the Incretin Hormones
Official title: Separate and Combined Extrapancreatic Effects of Glucose-dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pancreatectomy; Hyperglycemia
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2022-01-04
Enrollment: 13
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days
timeFrame: Up to two months
measure: Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days
timeFrame: Up to two months
measure: Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days
timeFrame: Up to two months
measure: Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days.
timeFrame: Up to two months
measure: Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days.
timeFrame: Up to two months
measure: Changes in brown adipose tissue activity between interventions, assessed by thermographic camera
timeFrame: Up to two months
measure: Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days.
timeFrame: Up to two months
measure: Changes in CTX between interventions assessed through frequently blood sampling during the experimental days
timeFrame: Up to two months
measure: Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days
timeFrame: Up to two months
Secondary outcomes:
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research
Study officials:
References: