Separate and Combined Extrapancreatic Effects of the Incretin Hormones

Pancreatectomy; Hyperglycemia Clinical Trial

— GA-19  

Official title:

Separate and Combined Extrapancreatic Effects of Glucose-dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05177653
• Other study ID #: H-21035117
• Status: Completed
• Phase: N/A
• Start date: April 7, 2022
• Est. completion date: March 3, 2023

Study information

• Verified date: March 2023
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 3, 2023
• Est. primary completion date: March 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperglycemia
• Pancreatectomy; Hyperglycemia

Intervention

Other:
• Intravenous infusion
GIP receptor antagonist (GIP(3-30)NH2)
• Intravenous infusion
GLP-1 receptor antagonist (exendin(9-39)NH2)
• Intravenous infusion
GIP(3-30)NH2 and exendin(9-39)NH2
• Intravenous infusion
Saline

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research	Hellerup

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days	mmol/l	Up to two months
Primary	Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days	pmol/l	Up to two months
Primary	Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days	pmol/l	Up to two months
Primary	Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days.	mmol/l lipoproteins, neutral and complex lipids.	Up to two months
Primary	Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days.	mg/dl	Up to two months
Primary	Changes in brown adipose tissue activity between interventions, assessed by thermographic camera		Up to two months
Primary	Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days.	µg/mL	Up to two months
Primary	Changes in CTX between interventions assessed through frequently blood sampling during the experimental days	ng/ml	Up to two months
Primary	Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days	ng/ml	Up to two months