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Trial record 2 of 2 for:    19362675 [PUBMED-IDS]

Treating Idiopathic Inflammatory Myopathies Related Reduced Bone Mineral Density With Denosumab or Zoledronic Acid

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ClinicalTrials.gov Identifier: NCT04034199
Recruitment Status : Not yet recruiting
First Posted : July 26, 2019
Last Update Posted : July 26, 2019
Sponsor:
Collaborator:
Tung Wah Group of Hospitals
Information provided by (Responsible Party):
Tang Yan Ki, Kwong Wah Hospital

Brief Summary:
Idiopathic inflammatory myopathies (IIM) patients are at high risk of development of reduced bone mineral density due to impairment of functional status due to the disease and a relatively high dose of glucocorticoid use for the treatment. Reduced bone mineral density is prevalent in local IIMs patients. Denosumab and zoledronic acid are established treatments for osteoporosis in postmenopausal women and glucocorticoid-induced osteoporosis. However, the role of these treatments in reduced bone mineral density including osteoporosis and osteopenia related to IIMs are lacking. There is also no evidence on comparing the efficacy of the two agents. Therefore, the investigators conducted this prospective randomized controlled study to compare the efficacies of denosumab and zoledronic acid in treating reduced bone mineral density in IIMs patients. The hypothesis in this study is that treatment by denosumab or zoledronic acid would improve bone mineral density in IIMs patients with reduced bone mineral density.

Condition or disease Intervention/treatment Phase
Idiopathic Inflammatory Myopathies Osteoporosis, Osteopenia Drug: Denosumab Drug: Zoledronic Acid Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a prospective open-label controlled trial. All patients will continue calcium (1000mg daily) and vitamin D supplementation (at least 800 international unit daily). Patients with osteopenia or osteoporosis in a baseline DEXA scan will be randomized by computer-generated blocks in 1:1 ratio into receiving denosumab (treatment group) or zoledronic acid (controlled group). Denosumab is given at 60mg subcutaneously every 6 months, following the FDA approved dosage. Zoledronic acid is administered intravenously at 5mg yearly. DEXA scan will be repeated after 12 months of treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Denosumab and Zoledronic Acid in the Treatment of Idiopathic Inflammatory Myopathies Related Reduced Bone Mineral Density: a Prospective Controlled Trial
Estimated Study Start Date : August 15, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : March 31, 2021


Arm Intervention/treatment
Experimental: Denosumab group
Patients randomized into the denosumab group will receive denosumab 60mg subcutaneously every 6 months, for a total duration of 1 year. DEXA scan would be repeated at 1 year.
Drug: Denosumab
Denosumab is a human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) and its use is associated with a reduced risk of vertebral, non-vertebral and hip fracture in post-menopausal women. RANKL plays a crucial role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). Its production is increased by GC, resulting in stimulated osteoprotegerin ligand production and increased bone resorption. Recent randomized controlled trial from Saag et al have shown that denosumab is more efficacious than risedronate in the improvement of BMD in GIOP patients. Denosumab has been confirmed efficacious in GIOP patients but its efficacy in high-risk osteopenia patients are not well studied. It is given subcutaneously at 60mg every 6 months.
Other Name: Prolia

Active Comparator: Zoledronic acid
Patients randomized into the denosumab group will receive one dose of zoledronic acid at 5mg intravenously. DEXA scan would be repeated at 1 year.
Drug: Zoledronic Acid
Zoledronic acid belongs to bisphosphonates and is licensed for the treatment of GIOP and 2 RCTs found zoledronic acid has superior efficacy in improvement in BMD at lumbar spine or femoral neck at 12 months when compared to risedronate. It is given intravenously every year at a dosage of 5mg.
Other Name: Aclasta




Primary Outcome Measures :
  1. Change in bone mineral density at 12 months in denosumab and zoledronic acid group [ Time Frame: 12 months ]
    The primary outcome is change in bone mineral density at lumbar spine and hip measured by DEXA between the denosumab and zoledronic acid groups compared to control group at 12 months. Differences in BMD between two groups is compared with paired t-test.


Secondary Outcome Measures :
  1. Prevalence of osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Prevalence of osteoporosis and osteopenia in idiopathic inflammatory myopathies patients at baseline. Osteoporosis is defined by a T score of <-2.5 on DEXA scan and osteopenia is defined by T score between -1.0 and -2.5 by DEXA scan.

  2. Comparison of Change in Bone Mineral Density at lumbar spine and hip between the two treatment groups (denosumab and zoledronic acid) [ Time Frame: 12 months ]
    Comparison of Change in Bone mineral density at lumbar spine and hip between the two treatment groups (denosumab and zoledronic acid), as measured by Dual energy X-ray absorptiometry (DEXA scan). Differences in BMD between two groups is compared with paired t-test.

  3. Gender as a risk factor for osteoporosis and osteopenia in IIMs patients [ Time Frame: at baseline ]
    Gender of participants would be recorded. Chi-square test will be used to compare categorical variables.

  4. Smoking status as a risk factor for osteoporosis and osteopenia in IIMs patients [ Time Frame: at baseline ]
    Smoking status (Never smoker, ex-smoker and current smoker) of the participantss would be recorded. Chi-square test will be used to compare categorical variables.

  5. Drinking status as a risk factor for osteoporosis and osteopenia in IIMs patients [ Time Frame: at baseline ]
    Drinking status (Nondrinker, Social drinker, ex-drinker and current drinker) of the participantss would be recorded. Units of alcohol comsumption per week would be recorded.

  6. Menopausal status as a risk factor for osteoporosis and osteopenia in IIMs patients [ Time Frame: at baseline ]
    In female patients, menopausal status (pre-menopausal and menopausal) would be recoded

  7. BMI as Risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Body weight and height will be combined to report Body Mass Index in kg/m^2. Continuous variables are expressed as mean +/- standard deviation if they are normally distributed or as median and range otherwise. Independent Student's t-test is used for analyzing continuous variables with normal distribution and Mann-Whitney U test for continuous variables without normal distribution.

  8. Age as Risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Age. Continuous variables are expressed as mean +/- standard deviation if they are normally distributed or as median and range otherwise. Independent Student's t-test is used for analyzing continuous variables with normal distribution and Mann-Whitney U test for continuous variables without normal distribution.

  9. IIMs disease duration as Risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Disease duration in years. Continuous variables are expressed as mean +/- standard deviation if they are normally distributed or as median and range otherwise. Independent Student's t-test is used for analyzing continuous variables with normal distribution and Mann-Whitney U test for continuous variables without normal distribution.

  10. Different subtypes of IIMs and risks for osteoporosis and osteopenia [ Time Frame: at baseline ]
    Classification of IIMs according to Bohan and Peter criteria and presence of co-morbidities including chronic kidney disease, chronic liver disease, cardiovascular disease and diabetes mellitus. Personal history of previous vertebral or osteoporotic fracture and avascular necrosis. Chi-square test will be used to compare categorical variables.

  11. Effect of medications on osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Drug history: Dosage of glucocorticoids (in milligram) at baseline and cumulative dose of glucocorticoids. Concomitant immunosuppressants and medication history.

  12. Serum albumin level as risk factor in osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Serum albumin level

  13. Serum C reactive protein level as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Serum C reactive protein level

  14. Erythrocyte sedimentation rate as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Erythrocyte sedimentation rate

  15. Serum creatine kinase as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Serum Creatine kinase level

  16. Disability as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    Health assessment questionnaire disability index at baseline

  17. Effect of IIMS disease activity on osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    IIMs disease activity at baseline is measured by physician's and patient's global assessment by visual analogue scale

  18. Effect of IIMs disease activity on osteoporosis and osteopenia in idiopathic inflammatory myopathies patients [ Time Frame: at baseline ]
    IIMs disease activity at baseline is measured by manual muscle testing 8

  19. New fractures during study period [ Time Frame: during study period (12 months) ]
    New fractures including lumbar spine collapses during study period in two groups will be documented.

  20. Adverse events associated with denosumab and zoledronic acid [ Time Frame: throughout study period (12 months) ]

    Occurence of adverse events and early termination of denosumab and zoledronic acid would be documented. The following events will be monitored and documented:

    Mortality during treatment period Serious adverse events including infection requiring hopitalization, cardiac failure, stroke, myocardial infarction.

    Adverse events related to treatment: atypical femoral fracture, osteonecrosis of the jaw, back pain, arthralgia & mylagia, injection site reaction and allergy. Serious treatment related adverse events are adverse events leading to discontinuation of treatment. Related symptoms are documented during every clinic follow-up visits. All patient's medical and hospitalization record during the study period will also be reviewed by the investigators.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

All idiopathic inflammatory myopathies (IIMs) patients under follow-up in Kwong Wah Hospital are invited to participate in this study.

IIMs are diagnosed by rheumatologist according to Bohan and Peter Criteria. Eligible patients will have dual-energy X-ray absorptiometry (DEXA) scan performed at baseline.

Inclusion Criteria:

  1. Adult patients of at least 18 years of age and
  2. Evidence of reduced BMD in osteopenia (defined by T-score of -0.1 to -2.5) or osteoporosis range (defined by T-score of < -2.5) at baseline by dual-energy X-ray absorptiometry (DEXA) scan.

Exclusion Criteria:

  1. Pregnant patients
  2. Patients with juvenile onset of disease (<18 years of age)
  3. Patients with pre-existing metabolic bone conditions
  4. Patients who are already on osteoporotic treatment other than calcium and vitamin D (including bisphosphonates, denosumab, teriparatide, raloxifene or strontium)
  5. Patients who are contraindicated to denosumab or zoledronic acid including severe renal impairment and hypersensitivity
  6. Patients who are not able to give informed consent

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): NCT04034199


Contacts
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Contact: Yan Ki Tang +852 35178320 tyk155@ha.org.hk

Locations
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Hong Kong
Kwong Wah Hospital Recruiting
Hong Kong, Hong Kong, 00000
Contact: Yan Ki Tang    +85235178320    tyk155@ha.org.hk   
Principal Investigator: Yan Ki Tang         
Sponsors and Collaborators
Kwong Wah Hospital
Tung Wah Group of Hospitals

Publications of Results:
Other Publications:

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Responsible Party: Tang Yan Ki, Principal investigator, Kwong Wah Hospital
ClinicalTrials.gov Identifier: NCT04034199     History of Changes
Other Study ID Numbers: kwh_rheumat_tyk_01
First Posted: July 26, 2019    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Tang Yan Ki, Kwong Wah Hospital:
denosumab
zoledronic acid
Additional relevant MeSH terms:
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Osteoporosis
Muscular Diseases
Bone Diseases, Metabolic
Myositis
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Neuromuscular Diseases
Nervous System Diseases
Zoledronic Acid
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs