Osteogenesis Imperfecta
Conditions
Keywords
Osteogenesis imperfecta, COL1A1/A2, Denosumab, Bisphosphonates, Children, Areal bone mineral density
Brief summary
Pilot study to assess the efficacy of a therapy with the RANKL-antibody denosumab in children 5-10 years of age with mutation in COL1A1 or COL1A2 leading to Osteogenesis imperfecta. Efficacy will be assessed by DXA measurements at the lumbar spine of the areal bone mineral density (BMD) which is the most frequently used parameter in trials investigating osteoporosis. The hypothesis of the study is: Osteoclastic activity which is increased in OI could be reduced by inhibition of osteoclast maturation. Denosumab inhibits maturation of the osteoclasts by inhibiting RANKL. BMD could be increased during a 36 week treatment course with denosumab measured after 48 weeks.
Interventions
DRUGDenosumab
Denosumab will be given subcutaneously in a dosage of 1mg/kg body weight every 12 weeks. 4 interventions are planned until trial week 36. There is no control group planned.
Sponsors
University of Cologne
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects between 5 years and 10 years of age with molecular proven Osteogenesis imperfecta (COL1A1/A2 mutation) * Subjects must have been treated for a minimum of 2 years with bisphosphonates prior to study entry
Exclusion criteria
* Hypocalcemia (\<1.03 mmol/l ionized Calcium) * Subjects with reduced renal function (estimated GFR (Schwartz formula) \<30ml/min/1.73m2) * Any other abnormal finding such as physical examination or laboratory evaluation, in the opinion of the investigator that is indicative of a disease that would compromise the safety of the patient when getting denosumab s.c.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes of bone mineral density (BMD [g/cm2]) in lumbar spine after 36 weeks of treatment with denosumab. Changes will be calculated between baseline and study week 48. | 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD). | 14 days (DPD) | — |
| Parathormone in study week 12, 24, 36 and 48 compared to baseline. | 12 weeks | Descriptive statistical analysis |
| N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline. | 12 weeks | descriptive statistical analysis |
| Osteocalcin in study week 12, 24, 36 and 48. | 12 weeks | descriptive statistical analysis |
Countries
Germany
Outcome results
None listed