Bone Disease, Metabolic, Diabetes Mellitus, Type 2, Obesity and Obesity-related Medical Conditions
Conditions
Keywords
GIP, CTX, P1NP, Glucose-dependent insulinotropic polypeptide, Bone remodelling
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.
Interventions
Recombinant human GIP (1-42)
Sponsors
Esbjerg Hospital - University Hospital of Southern Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum levels of CTX | During a three day period. With 14-28 days of washout between the two administration methods | Serum levels of CTX (bone resorption marker) will be measured prior to, during, and at after the intervention, with both administration methods (continious and intermittent) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum levels of osteocalcin and P1NP | During a three day period. With 14-28 days of washout between the two administration methods | Serum levels of osteocalcin and P1NP (bone formation markers) will be measured prior to, during, and at after the intervention, with both administration methods (continious and intermittent) |
| Serum levels of GIP | During a three day period. With 14-28 days of washout between the two administration methods | Serum levels of GIP will be measured prior to, during, and at after the intervention, with both administration methods (continious and intermittent) |
Countries
Denmark
Contacts
Primary ContactTobias Midtvedt Windedal, MD
Outcome results
None listed