Identifying Individuals at Risk of Glucocorticoid-Induced Impairment of Bone Disease (RIGID)

Previous studies have shown that there is a large inter-individual variability in the degree of bone loss during glucocorticoid treatment, and while some patients experience extensive bone loss other patients' bone mass remains stable. The aim of the study is to find a biomarker that can be used to identify individuals at risk of glucocorticoid-induced bone loss. The study will include 36 healthy volunteers, that will be randomized to receive either glucocorticoid treatment or placebo. During the study blood samples, bone marrow samples, bone tissue samples, and adipose tissue samples are taken and a mixed meal test is performed.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoporosis Secondary
• Intervention / Treatment: Drug: Prednisolone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Catharina Vind Nielsen, MD; Phone Number: +45 21351124; Email: catharina.vind.nielsen@rsyd.dk

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Hospital of South West Jutland
    • Contact: Catharina Vind Nielsen, MD; Phone Number: +45 21351124; Email: catharina.vind.nielsen@rsyd.dk
  • Odense C, Denmark, 5000
    • Odense University Hospital
    • Contact: Catharina Vind Nielsen, MD; Phone Number: +45 21351124; Email: catharina.vind.nielsen@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women aged 18-50 years.

Exclusion Criteria:

• Uncontrolled thyrotoxicosis
• Chronic kidney disease (eGFR <30)
• Known Cushing's syndrome
• Previous gastric bypass and/or known ongoing malabsorption
• Severe covid-19 in the last 3 month (defined as needing dexamethasone treatment)
• Use of oral or inhaled glucocorticoids within the past year
• Menopause (defined as 1 year without menstrual bleeding)
• Pregnancy (defined as elevated HCG)
• Ongoing infection
• Allergy to prednisolone or one of the excipients
• Systematic fungal infections
• Vaccination with living or weaken viral or bacterial vaccines in patient who or immunocompromised. In these cases, prednisolone treatment should not be administered two weeks before and after vaccination
• Not able to provide informed consent (e.g., dementia, not able to understand Danish).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group	Drug: Placebo; Placebo treatment for seven days
Experimental: Prednisolone group	Drug: Prednisolone; prednisoline 25 mg/day for seven days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procollagen type 1 N-terminal propeptide (P1NP)	Changes in the level of the bone turnover marker P1NP in peripheral blood from baseline to day 8	Baseline to day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collagen 1 cross link C-terminal telopeptide (CTX)	Changes in the level of the bone turnover marker CTX in peripheral blood from baseline to day 8 and 15	Baseline to day 8 and 15
P1NP (baseline to day 15)	Changes in the level of the bone turnover marker P1NP in peripheral blood from baseline to day 15	Baseline to day 15
Concentration of Glucocorticoid metabolites	Changes in the levels of glucocorticoid metabolites in blood from baseline to day 8	Baseline to day 8
Adipose tissue	Changes in gene expression in abdominal and gluteal subcutaneous adipose tissue from baseline to day 8	Baseline to day 8
Bone tissue	Changes in gene expression in bone tissue from baseline to day 8	Baseline to day 8
Glucose	Changes in glucose levels during a mixed meal test from baseline to day 8	Baseline to day 8
C-peptid	Changes in c-peptid levels during a mixed meal test from baseline to day 8	Baseline to day 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker	Untargeted proteomics will be used to try to identify a biomarker for individuals at risk of glucocorticoid induced bone loss	Baseline

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: University of Ulm; University of Birmingham; Hospital of South West Jutland
• Investigators: Principal Investigator: Morten Frost, MD, Odense University Hospital; Principal Investigator: Claus Bogh Juhl, MD, Hospital of South West Jutland

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases, Metabolic; Osteoporosis; Bone Diseases; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: 2023-506949-27-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with other researchers other than collaborators. Since the data contains personal information from the study participants

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No