Clinical trial NCT06790225: Glucose-dependent INsulinotropic Polypeptide: Effect on Bone Remodelling and Cell Activity (GINEBRA)
Official title: Glucose-dependent INsulinotropic Polypeptide: Effect on Bone Remodelling and Cell Activity (GINEBRA)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Bone Disease, Metabolic
Diabetes Mellitus, Type 2
Obesity and Obesity-related Medical Conditions
Keywords: GIP
CTX
P1NP
Glucose-dependent insulinotropic polypeptide
Bone remodelling
Lead sponsor: Esbjerg Hospital - University Hospital of Southern Denmark
Sponsor class: OTHER
First posted: 2025-01-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants are randomized to recive either intermittent ( 8 hours a day) or continious (24 hours a day) GIP infusion for three days. 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 using bone marrow aspirates and bone marrow biopsies. Each participant will recive both administrations using a crossover design with 14-28 days washout period inbetween.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Serum levels of CTX
timeFrame: During a three day period. With 14-28 days of washout between the two administration methods
Secondary outcomes:
measure: Serum levels of osteocalcin and P1NP
timeFrame: During a three day period. With 14-28 days of washout between the two administration methods
measure: Serum levels of GIP
timeFrame: During a three day period. With 14-28 days of washout between the two administration methods
Other outcomes:
Locations:
city: Esbjerg
country: Denmark
facility: University hospital of Southern Denmark
Study officials:
References: