Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders
Information source: Indiana University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Osteoporosis; Juvenile Rheumatoid Arthritis; Dermatomyositis; Polyarthritis; Systemic Lupus Erythematosis; Vasculitis; Glucocorticoid-induced Osteoporosis
Intervention: denosumab (Drug)
Phase: Phase 1/Phase 2
Status: Not yet recruiting
Sponsored by: Indiana University Official(s) and/or principal investigator(s): Erik Imel, MD, Principal Investigator, Affiliation: Indiana University
Overall contact: Marian Hart, Phone: 317-948-8346
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.
Clinical Details
Official title: Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders: a Pilot Study
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio).
Secondary outcome: The duration of suppression of the NTX/creatinine ratioThe changes in bone specific alkaline phosphorus Changes of BMD spine Z-scores Changes of BMD Total body less head (TBLH) Z-scores Changes of volumetric BMD on peripheral quantitative computed tomography Changes of polar strength-strain index at tibia Changes of polar strength-strain index at radius Changes in bone strength index for compression at tibia. Changes in bone strength index for compression at radius The relationships of Interleukin 6 to baseline NTX/creatinine ratio The relationships of Interleukin 6 to baseline DXA The relationships of Interleukin 6 to baseline pQCT variables. The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD Dose limiting toxicities (DLTs), including hypocalcemia
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.
Eligibility
Minimum age: 4 Years.
Maximum age: 16 Years.
Gender(s): Both.
Criteria:
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).
Locations and Contacts
Marian Hart, Phone: 317-948-8346
Indiana University School of Medicine, Indianapolis, Indiana 46202, United States
Additional Information
Starting date: June 2015
Last updated: April 13, 2015
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