Idiopathic Inflammatory Myopathies Clinical Trial
Official title:
Efficacy of Denosumab and Zoledronic Acid in the Treatment of Idiopathic Inflammatory Myopathies Related Reduced Bone Mineral Density: a Prospective Controlled Trial
Verified date | July 2019 |
Source | Kwong Wah Hospital |
Contact | Yan Ki Tang |
Phone | +852 35178320 |
tyk155[@]ha.org.hk | |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Not yet recruiting |
Enrollment | 40 |
Est. completion date | March 31, 2021 |
Est. primary completion date | December 31, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
Hong Kong | Kwong Wah Hospital | Hong Kong |
Lead Sponsor | Collaborator |
---|---|
Kwong Wah Hospital | Tung Wah Group of Hospitals |
Hong Kong,
Angeli A, Guglielmi G, Dovio A, Capelli G, de Feo D, Giannini S, Giorgino R, Moro L, Giustina A. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone. 2006 Aug;39(2):253-9. Epub 2006 Mar 30. — View Citation
Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. Review. — View Citation
Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403-7. Review. — View Citation
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11. Erratum in: N Engl J Med. 2009 Nov 5;361(19):1914. — View Citation
Curtis JR, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V, Kovac SH, Spettell CM, Saag KG. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006 Jun 15;55(3):420-6. — View Citation
Isenberg DA, Allen E, Farewell V, Ehrenstein MR, Hanna MG, Lundberg IE, Oddis C, Pilkington C, Plotz P, Scott D, Vencovsky J, Cooper R, Rider L, Miller F; International Myositis and Clinical Studies Group (IMACS). International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford). 2004 Jan;43(1):49-54. Epub 2003 Jul 16. Review. — View Citation
Liu M, Guo L, Pei Y, Li N, Jin M, Ma L, Liu Y, Sun B, Li C. Efficacy of zoledronic acid in treatment of osteoporosis in men and women-a meta-analysis. Int J Clin Exp Med. 2015 Mar 15;8(3):3855-61. eCollection 2015. — View Citation
Mok CC, Ho LY, Ma KM. Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: a 12-month randomized controlled trial. Bone. 2015 Jun;75:222-8. doi: 10.1016/j.bone.2015.03.002. Epub 2015 Mar 8. — View Citation
Mok CC, Ying KY, To CH, Ho LY, Yu KL, Lee HK, Ma KM. Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial. Ann Rheum Dis. 2011 May;70(5):778-84. doi: 10.1136/ard.2010.143453. Epub 2010 Dec 27. — View Citation
Reid DM, Devogelaer JP, Saag K, Roux C, Lau CS, Reginster JY, Papanastasiou P, Ferreira A, Hartl F, Fashola T, Mesenbrink P, Sambrook PN; HORIZON investigators. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced oste — View Citation
Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, Chapurlat R, Wang A, Pannacciulli N, Lems WF. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non — View Citation
So H, Yip ML, Wong AK. Prevalence and associated factors of reduced bone mineral density in patients with idiopathic inflammatory myopathies. Int J Rheum Dis. 2016 May;19(5):521-8. doi: 10.1111/1756-185X.12405. Epub 2014 May 21. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in bone mineral density at 12 months in denosumab and zoledronic acid group | 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. | 12 months | |
Secondary | Prevalence of osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | 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. | at baseline | |
Secondary | Comparison of Change in Bone Mineral Density at lumbar spine and hip between the two treatment groups (denosumab and zoledronic acid) | 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. | 12 months | |
Secondary | Gender as a risk factor for osteoporosis and osteopenia in IIMs patients | Gender of participants would be recorded. Chi-square test will be used to compare categorical variables. | at baseline | |
Secondary | Smoking status as a risk factor for osteoporosis and osteopenia in IIMs patients | 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. | at baseline | |
Secondary | Drinking status as a risk factor for osteoporosis and osteopenia in IIMs patients | 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. | at baseline | |
Secondary | Menopausal status as a risk factor for osteoporosis and osteopenia in IIMs patients | In female patients, menopausal status (pre-menopausal and menopausal) would be recoded | at baseline | |
Secondary | BMI as Risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | 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. | at baseline | |
Secondary | Age as Risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | 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. | at baseline | |
Secondary | IIMs disease duration as Risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | 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. | at baseline | |
Secondary | Different subtypes of IIMs and risks for osteoporosis and osteopenia | 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. | at baseline | |
Secondary | Effect of medications on osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | Drug history: Dosage of glucocorticoids (in milligram) at baseline and cumulative dose of glucocorticoids. Concomitant immunosuppressants and medication history. | at baseline | |
Secondary | Serum albumin level as risk factor in osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | Serum albumin level | at baseline | |
Secondary | Serum C reactive protein level as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | Serum C reactive protein level | at baseline | |
Secondary | Erythrocyte sedimentation rate as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | Erythrocyte sedimentation rate | at baseline | |
Secondary | Serum creatine kinase as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | Serum Creatine kinase level | at baseline | |
Secondary | Disability as risk factor for osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | Health assessment questionnaire disability index at baseline | at baseline | |
Secondary | Effect of IIMS disease activity on osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | IIMs disease activity at baseline is measured by physician's and patient's global assessment by visual analogue scale | at baseline | |
Secondary | Effect of IIMs disease activity on osteoporosis and osteopenia in idiopathic inflammatory myopathies patients | IIMs disease activity at baseline is measured by manual muscle testing 8 | at baseline | |
Secondary | New fractures during study period | New fractures including lumbar spine collapses during study period in two groups will be documented. | during study period (12 months) | |
Secondary | Adverse events associated with denosumab and zoledronic acid | 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. |
throughout study period (12 months) |
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