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Trial record 24 of 1096 for:    Recruiting, Not yet recruiting, Available Studies | "Glucocorticoids"

Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders

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ClinicalTrials.gov Identifier: NCT02418273
Recruitment Status : Not yet recruiting
First Posted : April 16, 2015
Last Update Posted : August 21, 2017
Sponsor:
Information provided by (Responsible Party):
Erik Imel, Indiana University

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

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 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
Experimental: Denosumab
These subjects will receive two sequential doses of denosumab
Drug: denosumab
These subjects will receive two doses of denosumab.
Other Name: Prolia

No Intervention: No drug intervention
These subjects do not receive denosumab



Primary Outcome Measures :
  1. 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 :
  1. The duration of suppression of the NTX/creatinine ratio [ Time Frame: up to six months after each dose day ]
  2. The changes in bone specific alkaline phosphorus [ Time Frame: From baseline to 1 week, 1,3,6 months after each dose day ]
  3. Changes of BMD spine Z-scores [ Time Frame: 12 month ]
  4. Changes of BMD Total body less head (TBLH) Z-scores [ Time Frame: 12 month ]
  5. Changes of volumetric BMD on peripheral quantitative computed tomography [ Time Frame: 12 month ]
  6. Changes of polar strength-strain index at tibia [ Time Frame: 12 month ]
  7. Changes of polar strength-strain index at radius [ Time Frame: 12 month ]
  8. Changes in bone strength index for compression at tibia. [ Time Frame: 12 month ]
  9. Changes in bone strength index for compression at radius [ Time Frame: 12 month ]
  10. The relationships of Interleukin 6 to baseline NTX/creatinine ratio [ Time Frame: baseline visit ]
  11. The relationships of Interleukin 6 to baseline DXA [ Time Frame: baseline visit ]
  12. The relationships of Interleukin 6 to baseline pQCT variables. [ Time Frame: baseline visit ]
  13. The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio [ Time Frame: baseline visit ]
  14. The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD [ Time Frame: baseline visit ]
  15. The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD [ Time Frame: baseline visit ]
  16. 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:

  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).

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


Contacts
Contact: Marian Hart 317-948-8346 marihart@iu.edu
Contact: Connie Sullivan 317-944-8431

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     History of Changes
Other Study ID Numbers: 1504269855
First Posted: April 16, 2015    Key Record Dates
Last Update Posted: August 21, 2017
Last Verified: August 2017

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:
denosumab
pediatric
rheumatology
osteoporosis
glucocorticoid

Additional relevant MeSH terms:
Glucocorticoids
Arthritis, Rheumatoid
Osteoporosis
Lupus Erythematosus, Systemic
Vasculitis
Dermatomyositis
Arthritis, Juvenile
Arthritis
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
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists