Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients (POSTOP)
The primary objective of the study is to examine the effect of denosumab on total hip bone mineral density (BMD) after one year of treatment in newly transplanted renal allograft recipients. Secondary endpoints include BMD changes at the lumbar spine and the femoral neck, changes in body height, changes in bone mineral metabolism parameters, incidence of fractures, and allograft function at one year. Safety measurements include the occurrence of rejection episodes, infectious complications, graft loss and mortality.
- Trial with medicinal product
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 3, Investigator-initiated, Randomized, Open-label Single-center Study of the Effect of Denosumab on the Prevention of Bone Mineral Density Loss After Renal Transplantation|
- Total hip bone mineral density (BMD) after one year of treatment [ Time Frame: Bone mineral density at 12 months ] [ Designated as safety issue: No ]
- Occurrence of fractures [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]BMD changes at the lumbar spine and the femoral neck, changes in body height, and changes in bone mineral metabolism parameters, incidence of fractures, allograft function at one year, occurrence of infections
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
60 mg denosumab s.c. at baseline and after 6 months
Drug: Denosumab (Prolia)
60 mg s.c. injection at baseline and after 6 months
Other Name: Prolia
|No Intervention: Control|
Renal allograft recipients are at high risk to suffer a substantial loss of bone mineral density (BMD) within the first year after kidney transplantation. This loss of BMD correlates with an increased risk for the development of osteoporosis or worsening of pre-existing osteopenia/osteoporosis, heightening the risk for the subsequent occurrence of fractures. Renal allograft recipients are often treated with calcium and vitamin D preparations to prevent BMD loss. The addition of bisphosphonates can further improve BMD. However, bisphosphonates are potentially nephrotoxic and promote adynamic bone disease, and are therefore not regularly prescribed.
Receptor Activator of Nuclear factor- Kappa-B Ligand (RANKL) is a key molecule mediating development, activity, and survival of osteoclasts. Osteoporosis results in part from increased osteoclastic bone resorption, and therefore the inhibition of RANKL activity has become an obvious therapeutic strategy to prevent bone mineral density (BMD) loss and the development of osteoporosis.
The novel anti-osteoporotic drug denosumab (trade name Prolia®) is a fully human monoclonal antibody against RANKL. By inhibiting the development and the activity as well as reducing the survival of osteoclasts it decreases bone resorption and increases bone density.
The hypothesis of the present study is that denosumab has a beneficial effect on the loss of BMD in the first year after renal transplantation. The preservation of BMD is a surrogate parameter, generally predicting subsequent improvements in the occurrence rate of fractures. The hypothesis will be tested by studying the effect of denosumab on BMD in newly transplanted renal allograft recipients.
The purpose of the present trial is to study the effect of denosumab on BMD in kidney allograft recipients. The study participants will be treated for 1 year, receiving a total of 2 injections of the standard 60 mg dose at baseline and at 6 months.
One-hundred sequential renal allograft recipients will be randomized 1:1 to receive two subcutaneous 60 mg denosumab injections within 14 days and 6 months following renal transplantation, or no treatment. All patients will also receive oral standard treatment with 1000 mg calcium plus 800 IU vitamin D.
|Contact: Rudolf P Wuthrich, MD||+41 44 255 33 firstname.lastname@example.org|
|Contact: Diana Frey, MD||+41 44 255 42 email@example.com|
|Division of Nephrology, University Hospital||Recruiting|
|Zurich, Switzerland, 8091|
|Contact: Rudolf P. Wuthrich, MD +41 44 255 33 84 firstname.lastname@example.org|
|Contact: Diana Frey, MD +41 44 255 42 12 email@example.com|
|Principal Investigator: Rudolf P. Wuthrich, MD|
|Sub-Investigator: Diana Frey, MD|
|Sub-Investigator: Jens Brockmann, MD|
|Principal Investigator:||Rudolf P Wuthrich, MD||Division of Nephrology, University Hospital, Zurich|