The Effect of GIP, GLP-1 and GLP-2 in Individuals With Genetically Altered Receptor Function (H-21044858)

University of Copenhagen

Status

Enrolling

Conditions

Incretin Effect

Treatments

Drug: GLP-1

Drug: GLP-2

Other: Placebo

Drug: GIP(1-42)

Study type

Interventional

Funder types

Other

Identifiers

NCT06194955

H-21044858

Details and patient eligibility

About

This project will characterize the physiological effect of the hormones, GIP-, GLP-1- and GLP-2 infusions in a group of individuals that are carriers of GIP-, GLP-1- and GLP-2 receptor gene variants, respectively.

Full description

Participants with mutations in their GLP-1- and GIP receptor will attend five randomized experimental days, A1, A2, B, C and D. On day A1 an oral glucose tolerance test (OGTT) will be performed, and on day A2, an intravenous isoglycaemic glucose infusion (IIGI) will be performed. On experimental day B and C, the study participants will receive GLP-1 and GIP hormones, respectively, under stable glucose infusions and on experimental day D, they will receive infusion of salt water (placebo) under stable glucose infusion.

Participants with mutations in their GLP-2 receptor will attend three randomized experimental days, E, F and G. A mixed meal test (MMT) will be performed on day E, an infusion with GLP-2 during fasting blood glucose levels will be performed on day F, and infusion with salt water (placebo) during fasting blood glucose levels will be performed on day G.

Additionally, a DXA scan and arginine test will be performed on all study participants.

Enrollment

60 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

BMI 19-35 kg/m2

Exclusion criteria

Treatment with medication or supplements that can not be discontinued for 12 hours
>10 objects of alcohol weekly or abuse of narcotics
Liver disease (defined as ALAT and/or ASAT ≥ 2 x normal levels)
Decreased kidney function (creatine levels over reference interval)
Uncontrollable increased blood pressure (> 140/90 mmHg)
Low blood percentage (hemoglobin < 8.3 mmol/l)
Special diet or planned weight change during trial period
Other conditions that could be expected to affect the primary or secondary outcomes

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Single Blind

60 participants in 6 patient groups, including a placebo group

GIPR variant carriers

Active Comparator group

Description:

Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.

Treatment:

Drug: GIP(1-42)

Drug: GLP-1

Other: Placebo

GIPR variant carrier controls

Placebo Comparator group

Description:

Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.

Treatment:

Drug: GIP(1-42)

Drug: GLP-1

Other: Placebo

GLP-1R variant carrier

Active Comparator group

Description:

Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp

Treatment:

Drug: GIP(1-42)

Drug: GLP-1

Other: Placebo

GLP-1R variant carrier controls

Placebo Comparator group

Description:

Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp.

Treatment:

Drug: GIP(1-42)

Drug: GLP-1

Other: Placebo

GLP-2R variant carrier

Active Comparator group

Description:

Individuals with GLP-2R variants: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels

Treatment:

Drug: GLP-2

Other: Placebo

GLP-2R variant carrier control

Placebo Comparator group

Description:

Healthy matched individuals: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels

Treatment:

Drug: GLP-2

Other: Placebo