Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients
Condition: Osteoporosis; Chronic Kidney Disease
MeSH terms: Osteoporosis; Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional
Phase: Phase 3

Summary: 
      The primary objective of the study is to examine the effect of denosumab on lumbar spine bone
      mineral density (BMD) after one year of treatment in newly transplanted renal allograft
      recipients. Secondary endpoints include BMD changes at the total hip 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
    

Detailed description: 
      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.

      Ninety 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.
    

Intervention name(s): Denosumab (Prolia)
Intervention type(s): Drug
Intervention description(s): 60 mg s.c. injection at baseline and after 6 months
Other intervention name(s): Prolia
Intervention MeSH terms: Denosumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Osteoporosis; Osteopenia; Denosumab; Transplantation; Kidney