Glucose-dependent INsulinotropic Polypeptide: Effect on Bone Remodelling and Cell Activity (GINEBRA)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Serum levels of CTX
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •healthy volunteers
Exclusion Criteria
- •pre-diabetes or diabetes (HbA1c >42mmol/mol)
- •fractures with < 6months
- •comorbidities/treatments that may influence bone metabolism or procedures - -- pregnancy
- •inability to provide informed concent
Arms & Interventions
Intermittent then continious
The participants that recive the intermittent administration first, followed by the continious
Intervention: Glucose-dependent Insulinotropic Polypeptide (GIP) (Other)
Continious then intermittent
The participants that recives the continious administration first, follwoed by the intermittent
Intervention: Glucose-dependent Insulinotropic Polypeptide (GIP) (Other)
Outcomes
Primary Outcomes
Serum levels of CTX
Time Frame: 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 Outcomes
- 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 GIP(During a three day period. With 14-28 days of washout between the two administration methods)