Separate and Combined Extrapancreatic Effects of the Incretin Hormones

NCT ID: NCT05177653

Last Updated: 2023-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-07
• Study Completion Date: 2023-03-03

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.

Conditions

Pancreatectomy; Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

GIPRA

Group Type: EXPERIMENTAL

Intravenous infusion

Intervention Type: OTHER

GIP receptor antagonist (GIP(3-30)NH2)

GLP-1RA

Group Type: EXPERIMENTAL

Intravenous infusion

Intervention Type: OTHER

GLP-1 receptor antagonist (exendin(9-39)NH2)

GIPRA + GLP-1RA

Group Type: EXPERIMENTAL

Intravenous infusion

Intervention Type: OTHER

GIP(3-30)NH2 and exendin(9-39)NH2

Saline

Group Type: PLACEBO_COMPARATOR

Intravenous infusion

Intervention Type: OTHER

Saline

Interventions

Intravenous infusion

GIP receptor antagonist (GIP(3-30)NH2)

Intervention Type: OTHER

Intravenous infusion

GLP-1 receptor antagonist (exendin(9-39)NH2)

Intervention Type: OTHER

Intravenous infusion

GIP(3-30)NH2 and exendin(9-39)NH2

Intervention Type: OTHER

Intravenous infusion

Saline

Intervention Type: OTHER

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Filip Krag Knop

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Center for Clinical Metabolic Research

Hellerup, , Denmark

Countries

Denmark

Other Identifiers

H-21035117

Identifier Type: -

Identifier Source: org_study_id