Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders
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| ClinicalTrials.gov Identifier: NCT02418273 |
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Recruitment Status :
Withdrawn
(was not funded)
First Posted : April 16, 2015
Last Update Posted : December 6, 2019
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Sponsor:
Indiana University
Information provided by (Responsible Party):
Erik Imel, Indiana University
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Osteoporosis Juvenile Rheumatoid Arthritis Dermatomyositis Polyarthritis Systemic Lupus Erythematosis Vasculitis Glucocorticoid-induced Osteoporosis | Drug: denosumab | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 0 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders: a Pilot Study |
| Estimated Study Start Date : | August 1, 2019 |
| Estimated Primary Completion Date : | June 2021 |
| Estimated Study Completion Date : | June 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Steroids
Drug Information available for:
Denosumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Denosumab
These subjects will receive two sequential doses of denosumab
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Drug: denosumab
These subjects will receive two doses of denosumab.
Other Name: Prolia |
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No Intervention: No drug intervention
These subjects do not receive denosumab
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Primary Outcome Measures :
- Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio). [ Time Frame: 2 weeks, 1 month, 2 month, 3 month after each dose day. ]
Secondary Outcome Measures :
- The duration of suppression of the NTX/creatinine ratio [ Time Frame: up to six months after each dose day ]
- The changes in bone specific alkaline phosphorus [ Time Frame: From baseline to 1 week, 1,3,6 months after each dose day ]
- Changes of BMD spine Z-scores [ Time Frame: 12 month ]
- Changes of BMD Total body less head (TBLH) Z-scores [ Time Frame: 12 month ]
- Changes of volumetric BMD on peripheral quantitative computed tomography [ Time Frame: 12 month ]
- Changes of polar strength-strain index at tibia [ Time Frame: 12 month ]
- Changes of polar strength-strain index at radius [ Time Frame: 12 month ]
- Changes in bone strength index for compression at tibia. [ Time Frame: 12 month ]
- Changes in bone strength index for compression at radius [ Time Frame: 12 month ]
- The relationships of Interleukin 6 to baseline NTX/creatinine ratio [ Time Frame: baseline visit ]
- The relationships of Interleukin 6 to baseline DXA [ Time Frame: baseline visit ]
- The relationships of Interleukin 6 to baseline pQCT variables. [ Time Frame: baseline visit ]
- The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio [ Time Frame: baseline visit ]
- The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD [ Time Frame: baseline visit ]
- The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD [ Time Frame: baseline visit ]
- Dose limiting toxicities (DLTs), including hypocalcemia [ Time Frame: 3 days, 1 week, 2, week, month 3,4,5,6 after each dose; or any other visits. ]
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| Ages Eligible for Study: | 4 Years to 16 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age 4 to 16 years of age.
- 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.
- Within 1 month of initiating glucocorticoids ≥0.5 mg/kg prednisone equivalent daily, planned for ≥ 6 months.
- BMD by DXA with Z-score < 0.0 on screening at lumbar spine or total body less head (TBLH).
Exclusion Criteria:
- Previous treatment with a bisphosphonate, or other osteoporosis medication.
- Metabolic bone disorders besides glucocorticoid-induced osteoporosis; other disorders treated with systemic glucocorticoids (inflammatory bowel disease, severe pulmonary disease, nephrotic syndrome, etc.).
- Intent to treat with a tumor necrosis factor inhibitor or Interleukin 6 receptor antagonist during the first 6 months.
- Glomerular filtration rate < 30ml/min [pediatric estimated glomerular filtration rate = 0.413*(height/serum creatinine)] 75
- Planned orthopedic or other major surgery during the course of the study (at the time of enrollment)
- Significant dental caries, or plans to undergo invasive oral procedures during the subsequent 12 months.
- Known allergy to latex (drug packaging includes a natural rubber stopper), fructose intolerance or other denosumab contraindication.
- 25-hydroxyvitamin D (25OHD) level < 32 ng/dl. Subjects with 25OHD <32 ng/ml may be given cholecalciferol and rescreened.
- Hypocalcemia at screening (total serum calcium < 8.5 mg/dl after correction for albumin level).
- Chronic ventilator dependence, or other conditions increasing risk of participation.
- Pregnancy, or refusal to use acceptable contraception or abstain during the protocol (post-pubertal female).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02418273
Locations
| United States, Indiana | |
| Indiana University School of Medicine | |
| Indianapolis, Indiana, United States, 46202 | |
Sponsors and Collaborators
Indiana University
Investigators
| Principal Investigator: | Erik Imel, MD | Indiana University |
| Responsible Party: | Erik Imel, Assistant Professor of Medicine and Pediatrics, Indiana University |
| ClinicalTrials.gov Identifier: | NCT02418273 |
| Other Study ID Numbers: |
1504269855 |
| First Posted: | April 16, 2015 Key Record Dates |
| Last Update Posted: | December 6, 2019 |
| Last Verified: | December 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Erik Imel, Indiana University:
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denosumab pediatric rheumatology osteoporosis glucocorticoid |
Additional relevant MeSH terms:
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Arthritis Osteoporosis Dermatomyositis Arthritis, Juvenile Vasculitis Lupus Erythematosus, Systemic Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Bone Diseases, Metabolic |
Bone Diseases Metabolic Diseases Vascular Diseases Cardiovascular Diseases Polymyositis Myositis Muscular Diseases Neuromuscular Diseases Nervous System Diseases Skin Diseases Denosumab Bone Density Conservation Agents Physiological Effects of Drugs |