The Effect of Semaglutide on Bone Turnover in Patients With Increased Risk of Bone Fracture
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Procollagen type 1 N-terminal propeptide (P1NP) [Baseline and 52 weeks]
Percentage changes in bone formation marker P1NP from baseline and after 12 months
Secondary Outcome Measures
- Collagen 1 cross link C-terminal telopeptide (CTX) [Baseline and 52 weeks]
Changes in bone resorption marker CTX from baseline and after 12 months
- Tartrate-resistant acid phosphatase (TRAP) [Baseline and 52 weeks]
Changes in bone resorption marker TRAP from baseline and after 12 months
- Osteocalcin [Baseline and 52 weeks]
Changes in bone formation marker osteocalcin from baseline and after 12 months
- Bone specific alkaline phosphatase (BALP) [Baseline and 52 weeks]
Changes in bone formation marker BALP from baseline and after 12 months
- BMSi [Baseline and 52 weeks]
Changes in direct bone strength measured by microindentation from baseline and after 12 months
- Bone mineral density (BMD) [Baseline and 52 weeks]
Changes in BMD (total hip, femoral neck and lumbar spine (L1-4)) assessed by DXA scans from baseline and after 12 months
- Estimated bone strength [Baseline and 52 weeks]
Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months
- Total volumetric BMD [Baseline and 52 weeks]
Changes in total volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius
- Trabecular volumetric BMD [Baseline and 52 weeks]
Changes in trabecular volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius
- Cortical volumetric BMD [Baseline and 52 weeks]
Changes in cortical volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius
- Bone volume [Baseline and 52 weeks]
Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius
- Trabecular thickness [Baseline and 52 weeks]
Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius
- Cortical thickness [Baseline and 52 weeks]
Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius
- Cortical porosity [Baseline and 52 weeks]
Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius
- Bone formation rate [52 weeks]
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
Other Outcome Measures
- Mirco RNAs [Baseline and 52 weeks]
Changes in expression of blood-circulating microRNAs (miRNAs) known to be involved in regulation of bone formation and bone resorption using qPCR
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Odense University Hospital | Odense | Region Of Southern Denmark | Denmark | 5000 |
Sponsors and Collaborators
- Morten Frost
- Hospital of South West Jutland
Investigators
- Principal Investigator: Morten Frost, MD, Odense University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- S-20200048
- 2020-000616-29
- 0052699
- 18/51856
- A35844