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

NCT06790225 | Recruiting

• 1 other identifier: 25/2685
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

GIP; CTX; P1NP; Glucose-dependent insulinotropic polypeptide; Bone remodelling

Outcome Measures

Primary Outcomes (1)

• Serum levels of CTX

  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)

  During a three day period. With 14-28 days of washout between the two administration methods

Secondary Outcomes (2)

• 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

Study Arms (2)

Intermittent then continious

EXPERIMENTAL

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

Other: Glucose-dependent Insulinotropic Polypeptide (GIP)

Continious then intermittent

EXPERIMENTAL

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

Other: Glucose-dependent Insulinotropic Polypeptide (GIP)

Interventions

Glucose-dependent Insulinotropic Polypeptide (GIP) OTHER

Recombinant human GIP (1-42)

Continious then intermittent; Intermittent then continious

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy volunteers

You may not qualify if:

• 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

Sponsors & Collaborators

• Esbjerg Hospital - University Hospital of Southern Denmark: lead

Study Sites (1)

University hospital of Southern Denmark

Esbjerg, 6700, Denmark

RECRUITING

MeSH Terms

Conditions

Bone Diseases, Metabolic; Diabetes Mellitus, Type 2; Obesity

Interventions

Incretins

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Tobias Midtvedt Windedal, MD

CONTACT

42957945; tobias.midtvedt.windedal@rsyd.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: January 24, 2025
• Study Start: November 10, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)