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

Phase 1
Conditions
Osteopenia
Interventions
Drug: Placebo
Registration Number
NCT04702516
Lead Sponsor
Morten Frost
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
64
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SemaglutideOzempicOzempic 1 mg (or highest tolerated dose) s.c. once weekly for 52 weeks (incl. titration)
PlaceboPlaceboPlacebo (saline) 1 mg (or highest tolerated dose) s.c. once weekly for 52 weeks (incl. titration)
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
BMSiBaseline 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 strengthBaseline and 52 weeks

Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months

Total volumetric BMDBaseline and 52 weeks

Changes in total volumetric BMD (mg/cm\^3) assessed by HR-pQCT scan of distal tibia and radius

Trabecular volumetric BMDBaseline and 52 weeks

Changes in trabecular volumetric BMD (mg/cm\^3) assessed by HR-pQCT scan of distal tibia and radius

Bone specific alkaline phosphatase (BALP)Baseline and 52 weeks

Changes in bone formation marker BALP from baseline and after 12 months

Bone volumeBaseline and 52 weeks

Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius

Tartrate-resistant acid phosphatase (TRAP)Baseline and 52 weeks

Changes in bone resorption marker TRAP from baseline and after 12 months

Collagen 1 cross link C-terminal telopeptide (CTX)Baseline and 52 weeks

Changes in bone resorption marker CTX from baseline and after 12 months

Cortical volumetric BMDBaseline and 52 weeks

Changes in cortical volumetric BMD (mg/cm\^3) assessed by HR-pQCT scan of distal tibia and radius

Trabecular thicknessBaseline and 52 weeks

Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius

Cortical thicknessBaseline and 52 weeks

Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius

OsteocalcinBaseline and 52 weeks

Changes in bone formation marker osteocalcin from baseline and after 12 months

Cortical porosityBaseline and 52 weeks

Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius

Bone formation rate52 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

Trial Locations

Locations (1)

Odense University Hospital

🇩🇰

Odense, Region Of Southern Denmark, Denmark

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