Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients
Information source: University of Zurich
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Osteoporosis; Chronic Kidney Disease
Intervention: Denosumab (Prolia) (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Rudolf Wuethrich Official(s) and/or principal investigator(s): Rudolf P Wuthrich, MD, Principal Investigator, Affiliation: Division of Nephrology, University Hospital, Zurich
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
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Lumbar spine bone mineral density (BMD) after one year of treatment
Secondary outcome: Occurrence of fractures
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
The key inclusion criteria are:
1. Male or female adult de novo kidney, kidney-pancreas or kidney-islet, or kidney-liver
transplant recipients
2. Functioning graft within 28 days after transplantation (creatinine having decreased
to <200 micromol/l without the need for dialysis)
3. Being on standard triple immunosuppression including a calcineurin antagonist
(cyclosporine or tacrolimus), mycophenolate (MMF or MPA) and steroids, with or
without induction treatment with basiliximab or anti-thymocyte globulin
Key exclusion criteria are:
1. Age <18 years
2. Rising creatinine after initial drop <200 micromol/l or creatinine >200 micromol/l at
baseline
3. Evidence of early acute rejection, either suspected clinically and/or proven by
biopsy
4. Presence of severe osteoporosis as evidenced by a T score <-4 at the hip, femoral
neck or any of the 4 vertebrae L1 to L4
5. Evidence of severe hyper- or hypoparathyroidism (iPTH >800 ng/l or <10 ng/l)
6. Hypocalcemia (total calcium <1. 8 mmol/l) or hypercalcemia (total calcium >2. 7 mmol/l)
7. Steroid-free de novo immunosuppression scheme
Locations and Contacts
Division of Nephrology, University Hospital, Zurich 8091, Switzerland
Additional Information
Starting date: June 2011
Last updated: July 28, 2014
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