Paget's disease of the bone (PDB) Musculoskeletal Diseases Paget's disease of bone [osteitis deformans]
Conditions
Interventions
Current interventions as of 26/06/2012:
Participants will be randomised to either infusions of zoledronic acid (Aclasta®) 5 mg by intravenous infusion over 15 minutes or placebo (0.9% saline) at basel
Sponsors
University of Edinburgh
Lothian NHS Board (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Both males and females are eligible for participation in this study. Genetic test: 1. Patients with PDB (probands): 1.1. Diagnosed with PDB 1.2. Have relatives older than 30 years who have not yet been diagnosed with PDB 2. Relatives: 2.1. Relatives are aged 30 years old or greater 2.2. Relatives not yet been diagnosed with PDB Intervention study: 1. Relatives of patients with SQSTM1 mutations 2. Aged 30 years old or greater 3. Carry SQSTM1 mutations 4. Not already diagnosed with PDB at study entry Observational study: 1. Relatives aged between 30 years old or greater 2. Relatives who on screening are found NOT to have SQSTM1 mutations
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 26/06/2012: Genetic test: For patients with PDB and relatives: 1. Subjects not willing to have a blood sample taken 2. Subjects who are unwilling or unable to consent. Intervention study: 1. Already diagnosed with PDB 2. Unwilling or unable to consent 3. Bisphosphonates contraindicated 4. Receiving bisphosphonate therapy for another reason 5. Severe liver or renal disease 6. Osteonecrosis of the jaw (ONJ) 7. If creatine clearance levels are less than 35 ml/min 8. Metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing 9. Active history of uveitis, iritis, or episcleritis 10. Already taking part in another randomised controlled clinical trial 11. Female patients of child bearing potential are eligible only if they are: 11.1. Not pregnant - negative pregnancy test on the day of or the day prior to the infusion 11.2. Consent to a pregnancy test prior to the inufsion 11.3. Non-lactating 11.4. Are sexually abstinent or are surgically sterile (tubal ligation or hysterectomy) 11.5. If sexually active: 11.5.1. Must receive specific advice from their consultant about possible risks associated with getting pregnant whilst on the trial, and 11.5.2. Must agree to practice a medically acceptable form of birth control for at least 12 months post infusion (acceptable birth control defined as the use of an intrauterine device [IUD], a barrier method with spermicide, condoms, subdermal implant or oral contraceptives) Previous exclusion criteria Genetic test: For patients with PDB and relatives: 1. Subjects not willing to have a blood sample taken 2. Subjects who are unwilling or unable to consent. Intervention study: 1. Already diagnosed with PDB 2. Unwilling or unable to consent 3. Bisphosphonates contraindicated 4. Receiving bisphosphonate therapy for another reason 5. Severe liver or renal disease 6. Osteonecrosis of the jaw (ONJ) 7. If creatine clearance levels are less than 35 ml/min 8. Metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing 9. Active history of uveitis, iritis, or episcleritis 10. Already taking part in another randomised controlled clinical trial 11. Female patients of child bearing potential are eligible only if they are: 11.1. Not pregnant - negative serum beta-human chorionic gonadotropin (b-hCG) pregnancy test done on the day, with results available, prior to infusion 11.2. Consent to a pregnancy test prior to every dose administration 11.3. Non-lactating 11.4. Are sexually abstinent or are surgically sterile (tubal ligation or hysterectomy) 11.5. If sexually active: 11.5.1. Must receive specific advice from their consultant about possible risks associated with getting pregnant whilst on the trial, and 11.5.2. Must agree to practice a medically acceptable form of birth control for at least 12 months post infusion (acceptable birth control defined as the use of an intrauterine device [IUD], a barrier method with spermicide, condoms, subdermal implant or oral contraceptives)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure (s): In the intervention study, the primary outcome will be the total number of subjects who develop new bone lesions between the baseline visit and the final follow up visit. In the observational study, the primary outcome measure will be anxiety / depression, measured using the HADS scale. Previous primary outcome measure (s): 1. Bone-lesion sub-study: total number of subjects who develop new bone lesions after 5 years 2. Biochemical marker sub-study: the development of elevated bone turnover over 3 years, as measured by alkaline phosphatase (ALP) 3. Observational study: anxiety/depression over 3 years, measured using the Hospital Anxiety and Depression Scale (HADS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measure (s): In the interventional study, the secondary outcome measures will be: 1. The development of elevated bone turnover, as measured by ALP and other biochemical markers of bone turnover. 2. Quality of life, and anxiety and depression assessed by the SF-36, BPI and HADS questionnaires. In the observational study, the secondary outcomes will be: 1. The development of elevated bone turnover, as measured by ALP and other biochemical markers of bone turnover. 2. Quality of life, assessed by the SF-36 questionnaire. Previous secondary outcome measure (s): 1. Biochemical marker study: 1.1. Patients will be followed up for 5 years and investigated for the development of bone lesions. At the end of study, we will perform a pooled analysis of data from the bone lesion sub-study and biochemical markers sub-study to determine if there is an overall effect of treatment on bone lesions 2. Biochemical and bone-lesion sub-study: 2.1. Quality of life, anxiety and depression assessed by the 36-item short form health survey (SF-36), Brief Pain Inventory (BPI) and HADS questionnaires at baseline and annually for 5 years 3. Observational sub-study: 3.1. Development of elevated bone turnover, as measured by ALP (blood sample) at baseline and once a year for 5 years 3.2. Quality of life, assessed by the SF-36 questionnaire at baseline and annually for 5 years | — |
Countries
Australia, Belgium, Ireland, Italy, New Zealand, Scotland, Spain, United Kingdom
Outcome results
None listed