Glucose-dependent INsulinotropic Polypeptide: Effect on Bone Remodelling and Cell Activity (GINEBRA)

Esbjerg Hospital - University Hospital of Southern Denmark

Status: Enrolling

Conditions: Bone Disease, Metabolic; Obesity and Obesity-related Medical Conditions; Diabetes Mellitus, Type 2

Treatments: Other: Glucose-dependent Insulinotropic Polypeptide (GIP)

Study type: Interventional

Funder types: Other

Identifiers

NCT06790225

25/2685

Details and patient eligibility

About

Glucose-dependent insulinotropic polypeptide (GIP) is released by the intestines in response to food intake and increases insulin secretion. Although short-term (< 3 hours) stimulation with GIP decreases bone resorption in humans, the effect may vanish following continuous administration within 24 hours, at least in patients with type 1 diabetes. Whether the anti-resorptive effect of GIP can be maintained if the hormone is non-continuously administrated is unclear. As the first GIP receptor (GIPR) agonist, tirzepatide was recently approved for the treatment of obesity and type 2 diabetes in the USA and type 2 diabetes alone in the EU, there is a need to establish knowledge about the long-term effects of GIP on bone health, including if different exposure times to GIP have different skeletal effects.

This project will investigate whether GIP maintains its anti-resorptive potential if given as intermittent compared to continuous infusion in healthy men and women aged 18-40 years. Administration cycles involve intermittent (8 hours daily) and continuous (24 hours daily) injection of GIP for three days each. The effect of GIP will be measured by bone markers in blood samples, as well as in vitro activity and genetic alterations of bone cells (osteoclasts and osteoblasts) using bone marrow aspirates and bone marrow biopsies. Each participant will receive both administration cycles using a crossover design with a 14-28 days washout period between administrations of GIP.

Enrollment: 12 estimated patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• healthy volunteers

Exclusion criteria

• pre-diabetes or diabetes (HbA1c >42mmol/mol)
• BMI >28
• fractures with < 6months
• comorbidities/treatments that may influence bone metabolism or procedures - -- pregnancy
• inability to provide informed concent

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Intermittent then continious

Experimental group

Description:

The participants that recive the intermittent administration first, followed by the continious

Treatment:

Other: Glucose-dependent Insulinotropic Polypeptide (GIP)

Continious then intermittent

Experimental group

Description:

The participants that recives the continious administration first, follwoed by the intermittent

Treatment:

Other: Glucose-dependent Insulinotropic Polypeptide (GIP)