The Effect of Semaglutide on Bone Turnover in Patients With Increased Risk of Bone Fracture

The Effect of Semaglutide (Ozempic) on Bone Turnover in Patients With Increased Fracture Risk: a Randomized Placebo-controlled Clinical Trial

The hypothesis for this study is that the GLP-1Ra Semaglutide has a positive effect on the balance between build-up and degradation as well as the strength of the bones in men and women aged 40-85 years at increased risk of bone fractures. Treatment involves injection of Semaglutide 1.34 mg/ml once a week or corresponding volume of placebo once a week for 52 weeks. The effect will be measured by bone markers in blood samples, bone scans, bone tissue tests (bone biopsy), and direct bone strength measured by microindentation at the start and end of the study.

Study Overview

• Status: Recruiting
• Conditions: Osteopenia
• Intervention / Treatment: Drug: Ozempic; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Morten Steen Svarer Hansen, MD; Phone Number: +4521249531; Email: morten.steen.hansen@rsyd.dk
• Study Contact Backup: Name: Morten Frost, MD; Email: mmfnielsen@health.sdu.dk

Study Locations

• Denmark
  • Region Of Southern Denmark
    • Odense, Region Of Southern Denmark, Denmark, 5000
      • Recruiting
      • Odense University Hospital
      • Contact: Morten Steen Hansen, MD; Phone Number: +4521249531; Email: morten.steen.hansen@rsyd.dk
      • Contact: Morten Frost, MD; Phone Number: +4522877448; Email: mmfnielsen@health.sdu.dk
      • Principal Investigator: Morten Frost, MD
      • Sub-Investigator: Morten Steen Hansen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• T-score <-1 in hip or lower back, assessed by DXA scan and / or
• Low-energy fracture within the last 3 years

Exclusion Criteria:

• T-score <-2.5 in hip or lower back, assessed by DXA scan, although these individuals may be included if they prefer to participate or are not candidates for conventional therapy, e.g., by eGFR <35 or adverse reaction (influenza-like symptoms, allergic reaction, etc.) to, e.g., bisphosphonate therapy
• Diabetes type 1 and 2
• Heart failure similar to NYHA Class IV
• Primary hyperparathyroidism
• Vitamin D deficiency (<25 nM) (re-test after substitution acceptable)
• Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR <20) or liver function (baseline phosphatase higher than twice upper limit (105 U/L)), rheumatism, celiac disease, hypogonadism, severe COPD, hypopituitarism, Cushing's disease
• Antiresorptive or bone anabolic drugs for the last 12 months
• Use of anabolic steroids in the previous year
• History of pancreatitis
• Allergy to the medicines used
• Inability to give informed consent
• BMI <20 kg / m2

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
Experimental: Semaglutide; Ozempic 1 mg (or highest tolerated dose) s.c. once weekly for 52 weeks (incl. titration)	Drug: Ozempic; 2 mg prefilled pen for subcutaneous injection, 0.25 mg for two weeks then 0.5 mg for two weeks and then 1 mg for another 48 weeks.
Placebo Comparator: Placebo; Placebo (saline) 1 mg (or highest tolerated dose) s.c. once weekly for 52 weeks (incl. titration)	Drug: Placebo; 2 mg prefilled pen for subcutaneous injection, 0.25 mg for two weeks then 0.5 mg for two weeks and then 1 mg for another 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procollagen type 1 N-terminal propeptide (P1NP)	Percentage changes in bone formation marker P1NP from baseline and after 12 months	Baseline and 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collagen 1 cross link C-terminal telopeptide (CTX)	Changes in bone resorption marker CTX from baseline and after 12 months	Baseline and 52 weeks
Tartrate-resistant acid phosphatase (TRAP)	Changes in bone resorption marker TRAP from baseline and after 12 months	Baseline and 52 weeks
Osteocalcin	Changes in bone formation marker osteocalcin from baseline and after 12 months	Baseline and 52 weeks
Bone specific alkaline phosphatase (BALP)	Changes in bone formation marker BALP from baseline and after 12 months	Baseline and 52 weeks
BMSi	Changes in direct bone strength measured by microindentation from baseline and after 12 months	Baseline and 52 weeks
Bone mineral density (BMD)	Changes in BMD (total hip, femoral neck and lumbar spine (L1-4)) assessed by DXA scans from baseline and after 12 months	Baseline and 52 weeks
Estimated bone strength	Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months	Baseline and 52 weeks
Total volumetric BMD	Changes in total volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Trabecular volumetric BMD	Changes in trabecular volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Cortical volumetric BMD	Changes in cortical volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Bone volume	Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Trabecular thickness	Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Cortical thickness	Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Cortical porosity	Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius	Baseline and 52 weeks
Bone formation rate	Changes in bone formation rate (BRF/BS, µm^3/µm^2 per day), the volume of mineralized bone made per unit surface of bone per year	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mirco RNAs	Changes in expression of blood-circulating microRNAs (miRNAs) known to be involved in regulation of bone formation and bone resorption using qPCR	Baseline and 52 weeks

Collaborators and Investigators

• Sponsor: Morten Frost
• Collaborators: Hospital of South West Jutland
• Investigators: Principal Investigator: Morten Frost, MD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Anticipated): August 31, 2022
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 26, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic
• Other Study ID Numbers: S-20200048; 2020-000616-29 (EudraCT Number); 0052699 (Other Grant/Funding Number: Novo Nordisk Foundation); 18/51856 (Other Grant/Funding Number: Region of Southern Denmark); A35844 (Other Grant/Funding Number: Gangsted Foundation)

Drug and device information, study documents

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