OsteoporosisPhase 1/2NCT02418273
Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders
A Phase 1/2 study testing denosumab in people with Osteoporosis and Juvenile Rheumatoid Arthritis, run by Indiana University at 1 site in United States.
Trial 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)… Read more about this study
- Who is it for?
- Ages 4 to 16 years
- Conditions the study is for
- Osteoporosis, Juvenile Rheumatoid Arthritis, Dermatomyositis
- What is being tested?
- denosumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2019to Jun 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 11Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University School of Medicine
Indianapolis, Indiana, 46202
About this study
Official title: Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders: a Pilot Study
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.
Read the 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.
- Conditions
- Osteoporosis, Juvenile Rheumatoid Arthritis, Dermatomyositis, Polyarthritis, Systemic Lupus Erythematosis, Vasculitis
- Being tested
- denosumab
- Keywords
- denosumab, pediatric, rheumatology, osteoporosis, glucocorticoid
- Medical subject headings
- Osteoporosis, Arthritis, Juvenile, Dermatomyositis, Arthritis, Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
denosumabDrug
Also called Prolia
These subjects will receive two doses of denosumab.
| Study group | Role | What they receive |
|---|---|---|
| Denosumab | Experimental | These subjects will receive two sequential doses of denosumab Receives: Drug: denosumab |
| No drug intervention | No intervention | These subjects do not receive denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio).
Measured: 2 weeks, 1 month, 2 month, 3 month after each dose day.
Secondary outcomes (16)
The duration of suppression of the NTX/creatinine ratio
Measured: up to six months after each dose day
The changes in bone specific alkaline phosphorus
Measured: From baseline to 1 week, 1,3,6 months after each dose day
Changes of BMD spine Z-scores
Measured: 12 month
Changes of BMD Total body less head (TBLH) Z-scores
Measured: 12 month
Changes of volumetric BMD on peripheral quantitative computed tomography
Measured: 12 month
Changes of polar strength-strain index at tibia
Measured: 12 month
Changes of polar strength-strain index at radius
Measured: 12 month
Changes in bone strength index for compression at tibia.
Measured: 12 month
Changes in bone strength index for compression at radius
Measured: 12 month
The relationships of Interleukin 6 to baseline NTX/creatinine ratio
Measured: baseline visit
The relationships of Interleukin 6 to baseline DXA
Measured: baseline visit
The relationships of Interleukin 6 to baseline pQCT variables.
Measured: baseline visit
The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio
Measured: baseline visit
The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD
Measured: baseline visit
The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD
Measured: baseline visit
Dose limiting toxicities (DLTs), including hypocalcemia
Measured: 3 days, 1 week, 2, week, month 3,4,5,6 after each dose; or any other visits.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2015 (estimated)
- Study start1 Aug 2019 (estimated)
- Primary completionJun 2021 (estimated)
- Study completionJun 2021 (estimated)
Why it stopped: was not funded
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erik Imel, Indiana University
- Investigators
- Erik Imel, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02418273
- Sponsor's protocol ID
- 1504269855
- Status last verified
- Dec 2019
- First submitted
- 6 Apr 2015
- Last updated
- 6 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders: a Pilot Study
- ClinicalTrials.gov ID
- NCT02418273
- Acronym / sponsor ID
- 1504269855
- Conditions
- Osteoporosis, Juvenile Rheumatoid Arthritis, Dermatomyositis, Polyarthritis, Systemic Lupus Erythematosis, Vasculitis
- Keywords
- denosumab, pediatric, rheumatology, osteoporosis, glucocorticoid
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: was not funded
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 1 Aug 2019 (estimated)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 16 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Experimental | Drug: denosumabThese subjects will receive two sequential doses of denosumab |
| No drug intervention | No intervention | –These subjects do not receive denosumab |
Who may qualify
- Ages
- 4 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| denosumabAlso: ProliaThese subjects will receive two doses of denosumab. | Drug | Denosumab |
Primary outcome
Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio).
Time frame: 2 weeks, 1 month, 2 month, 3 month after each dose day.
16 secondary outcomes
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2019.
Related trials for Osteoporosis
RecruitingObservational study
A Clinical Study to Collect Real-wordt Data on Safety and Clinical Performance of the VCFix Spinal System for Treatment of Vertebral Compression Fractures of (Suspected) Osteoporotic Origin.
Vertebra Compression Fracture
Active, not recruitingObservational study
The Impact of Osteosarcopenia on Falls, Kinesiophobia, and Quality of Life in Postmenopausal Women
Osteosarcopenia, Sarcopenia
Active, not recruitingPhase 2
TCM Formula vs. HMB in Pre-Frail Elders: Muscle Strength and Bone Status
Pre-Frailty, Sarcopenia
Not yet recruitingPhase 4
Romosozumab and Denosumab Combination Therapy for Osteoporosis
Postmenopausal Osteoporosis
RecruitingObservational study
Assessment and Comparison of Osteoporosis Risk Factors After Stroke
Stroke, Osteoporosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erik Imel, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing denosumab in people with Osteoporosis and Juvenile Rheumatoid Arthritis, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio). (time frame: 2 weeks, 1 month, 2 month, 3 month after each dose day.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2019.