Dermatomyositis, Glucocorticoid-induced Osteoporosis, Juvenile Rheumatoid Arthritis, Osteoporosis, Polyarthritis, Systemic Lupus Erythematosis, Vasculitis
Conditions
Keywords
denosumab, pediatric, rheumatology, osteoporosis, glucocorticoid
Brief summary
The purpose of this study is to evaluate denosumab as a novel treatment for bone loss in children treated with glucocorticoids for rheumatic disorders. This is a pilot Phase 1/2, randomized open-label, 12-month clinical trial of denosumab to assess its effect on bone resorption markers and bone mineral density (BMD) in children with rheumatic disorders, age 4 to 16 years, recruited within 1 month of starting a chronic systemic glucocorticoid regimen. Primary outcomes include suppression of bone turnover markers and safety assessments. Secondary outcomes include changes in bone density as measured by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) densitometry at the radius and tibia.
Detailed description
The purpose of this study is to evaluate denosumab as a novel treatment for bone loss in children treated with glucocorticoids for rheumatic disorders. Children with rheumatic disorders are at risk for low bone density and fractures from the inflammatory effects of the underlying disease, and also from direct effects of glucocorticoids on bone. This is a pilot Phase 1/2, randomized open-label, 12-month clinical trial of denosumab to assess its effect on bone resorption markers and BMD in children with rheumatic disorders, age 4 to 16 years, recruited within 1 month of starting a chronic systemic glucocorticoid regimen. Two different sequential doses will be administered to the intervention group and evaluation for safety and efficacy will be conducted at study visits. Primary outcomes include suppression of bone turnover markers and safety assessments. Secondary outcomes include changes in bone density as measured by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) densitometry at the radius and tibia.
Interventions
DRUGdenosumab
These subjects will receive two doses of denosumab.
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. Age 4 to 16 years of age. 2. Diagnosis of one of the following by a rheumatologist using standard criteria: juvenile dermatomyositis, juvenile idiopathic arthritis, systemic arthritis, seronegative or seropositive polyarthritis, psoriatic arthritis, systemic lupus or systemic vasculitis. 3. Within 1 month of initiating glucocorticoids ≥0.5 mg/kg prednisone equivalent daily, planned for ≥ 6 months. 4. BMD by DXA with Z-score \< 0.0 on screening at lumbar spine or total body less head (TBLH).
Exclusion criteria
1. Previous treatment with a bisphosphonate, or other osteoporosis medication. 2. Metabolic bone disorders besides glucocorticoid-induced osteoporosis; other disorders treated with systemic glucocorticoids (inflammatory bowel disease, severe pulmonary disease, nephrotic syndrome, etc.). 3. Intent to treat with a tumor necrosis factor inhibitor or Interleukin 6 receptor antagonist during the first 6 months. 4. Glomerular filtration rate \< 30ml/min \[pediatric estimated glomerular filtration rate = 0.413\*(height/serum creatinine)\] 75 5. Planned orthopedic or other major surgery during the course of the study (at the time of enrollment) 6. Significant dental caries, or plans to undergo invasive oral procedures during the subsequent 12 months. 7. Known allergy to latex (drug packaging includes a natural rubber stopper), fructose intolerance or other denosumab contraindication. 8. 25-hydroxyvitamin D (25OHD) level \< 32 ng/dl. Subjects with 25OHD \<32 ng/ml may be given cholecalciferol and rescreened. 9. Hypocalcemia at screening (total serum calcium \< 8.5 mg/dl after correction for albumin level). 10. Chronic ventilator dependence, or other conditions increasing risk of participation. 11. Pregnancy, or refusal to use acceptable contraception or abstain during the protocol (post-pubertal female).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio). | 2 weeks, 1 month, 2 month, 3 month after each dose day. |
Secondary
| Measure | Time frame |
|---|---|
| Changes of BMD Total body less head (TBLH) Z-scores | 12 month |
| The duration of suppression of the NTX/creatinine ratio | up to six months after each dose day |
| The changes in bone specific alkaline phosphorus | From baseline to 1 week, 1,3,6 months after each dose day |
| Changes of volumetric BMD on peripheral quantitative computed tomography | 12 month |
| Changes of polar strength-strain index at tibia | 12 month |
| Changes of polar strength-strain index at radius | 12 month |
| Changes in bone strength index for compression at tibia. | 12 month |
| Changes of BMD spine Z-scores | 12 month |
| The relationships of Interleukin 6 to baseline NTX/creatinine ratio | baseline visit |
| The relationships of Interleukin 6 to baseline DXA | baseline visit |
| The relationships of Interleukin 6 to baseline pQCT variables. | baseline visit |
| The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio | baseline visit |
| The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD | baseline visit |
| The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD | baseline visit |
| Dose limiting toxicities (DLTs), including hypocalcemia | 3 days, 1 week, 2, week, month 3,4,5,6 after each dose; or any other visits. |
| Changes in bone strength index for compression at radius | 12 month |
Countries
United States
Outcome results
None listed