Osteogenesis imperfecta Musculoskeletal Diseases Osteogenesis imperfecta
Conditions
Interventions
This is a Phase II/pilot, open-label dose-escalating study. The final dose is randomly assigned. This study aims to identify the “effective” dose for losartan in this population to inform the design
Sponsors
Sheffield Children's NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
16 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Age 16 years and above 2. Diagnosed with osteogenesis imperfecta (any type) 3. Prior treatment with up to and including 6 weeks of oral bisphosphonate therapy is allowed provided there has been a 6-month washout period since the last dose of treatment 4. Prior treatment with a single dose of an intravenous bisphosphonate is allowed provided there has been a 6-month washout period since the treatment was given 5. Prior treatment with a single dose of denosumab is allowed provided there has been a 6-month washout period since the treatment was given 6. A woman of childbearing potential (WOCBP) who agrees to use an effective method of contraception from point of signing the informed consent throughout the study 7. Agreed not to participate in another interventional research project during their involvement in this study 8. Not taking prohibited concomitant medications, listed in exclusion criteria 9. Any other contraindication that makes the patient unsuitable to take part in the study in the opinion of the investigator
Exclusion criteria
Exclusion criteria: 1. Current use of losartan 2. Prior use of losartan within the preceding 6 months to enrolment 3. Presence of other chronic illnesses including renal failure likely to affect bone metabolism or structure 4. Known severe hypotension resulting in dizziness, fainting or headaches 5. Hyperkalaemia 6. Current medication that increases potassium retention, or may increase potassium levels, such as potassium-retaining diuretics 7. Current medication with lithium 8. Current medication with other substances which may induce hypotension 9. Currently taking oral bisphosphonates or intravenous bisphosphonates 10. Prior treatment with more than 6 weeks oral bisphosphonates treatment 11. Prior treatment with more than a single dose of intravenous bisphosphonate 12. Prior treatment with more than one dose of denosumab 13. Recent (last 12 months) or current treatment likely to affect bone – this does not include inhaled or intermittent oral therapy with steroids for asthma (no more than 3 months of oral steroids in previous 12 months) 14. Severe hepatic impairment 15. Renal impairment (glomerular filtration rate [GFR] <60 ml/min/m²) if treated with aliskiren-containing products 16. Diabetes mellitus if treated with aliskiren-containing products 17. Cardiac failure treated with diuretics 18. Pregnancy or lactation 19. Known hypersensitivity to losartan or any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage change in CTX over the 24-week period of the study, measured by a fasting blood test on Day 1 and Weeks 1, 4, 8, and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Percentage change in TGFß, measured by a fasting blood test on Day 1, Weeks 1, 4, 8, 24 and early withdrawal visit 2. Change in dual x-ray absorptiometry (DXA) lumbar spine and hip measured by DXA lumbar spine areal bone mineral density (LSaBMD) scans on Day 1, Week 24 and early withdrawal visit (after week 12) 3. Change in radial and tibial total vBMD measured by HRpQCT at Day 1, Week 24 and early withdrawal visit (after week 12) 4. Change in Timed Up and Go test measured by a “Timed up and go” test on Day 1, Week 8, 24 and early withdrawal visits 5. Change in osteogenesis imperfecta (OI) QoL measured by a OI quality of life questionnaire at Day 1, Week 8, 16, 24 and early withdrawal visits | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed