Paricalcitol in Reducing Parathyroid Hormone Levels and Ameliorating Markers of Bone Remodelling in Renal Transplant Recipients With Secondary Hyperparathyroidism
Condition: Renal Transplant; Secondary Hyperparathyroidism
MeSH terms: Neoplasm Metastasis; Hyperparathyroidism; Hyperparathyroidism, Secondary
Study type: Interventional
Phase: Phase 2

Summary: 
      The risk of fracture for kidney transplant recipients is 4 times higher that of the general
      population. The hyperparathyroidism plays a key role in the maintenance or development of
      post-transplant alterations of bone remodelling.

      Renal transplant patients are at high risk of hyperparathyroidism, largely because of
      long-lasting renal insufficiency before transplant, and of progressive deterioration of
      kidney function because of chronic allograft nephropathy (a disease of proteinuria and
      progressive decline of the glomerular filtration rate).In hemodialysis patients, intravenous
      paricalcitol (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster
      and more effective normalization of parathyroid hormone (PTH) levels than calcitriol
      (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum
      calcium and phosphorus levels.

      Whether oral paricalcitol may help achieving a prompt reduction in serum PTH levels and,
      secondarily, in urinary protein excretion in renal transplant recipients with secondary
      hyperparathyroidism is worth investigating.
    

Detailed description: 
      BACKGROUND The risk of fracture for kidney transplant recipients is 4 times higher that of
      the general population. The pathogenesis of post-transplant bone disease is multifactorial,
      but hyperparathyroidism plays a key role in the maintenance or development of post-transplant
      alterations of bone remodelling. Vitamin D and its analogues are key components of treatment
      aimed to prevent or ameliorate secondary hyperparathyroidism in patients with chronic kidney
      disease (CKD). In hemodialysis patients, intravenous paricalcitol
      (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster and more
      effective normalization of parathyroid hormone (PTH) levels than calcitriol
      (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum
      calcium and phosphorus levels. Preliminary evidence is also available that in pre-dialysis
      patients with CKD and secondary hyperparathyroidism, treatment with oral paricalcitol may
      also reduce urinary protein excretion, an effect that is independent of concomitant treatment
      with agents that block the renin-angiotensin system and that in the long-term might translate
      into slower progression to end stage kidney disease and need for renal replacement therapy.

      Renal transplant patients are at high risk of hyperparathyroidism, largely because of
      long-lasting renal insufficiency before transplant, and of progressive deterioration of
      kidney function because of chronic allograft nephropathy (a disease of proteinuria and
      progressive decline of the glomerular filtration rate). Whether oral paricalcitol may help
      achieving a prompt reduction in serum PTH levels and, secondarily, in urinary protein
      excretion in renal transplant recipients with secondary hyperparathyroidism is worth
      investigating.

      AIMS Primary To evaluate whether 6-months treatment with paricalcitol may achieve a prompt
      and effective reduction in PTH serum levels in stable renal transplant patients with
      secondary hyperparathyroidism.

      DESIGN This will be a Prospective, Randomized, Open label, Cross-over study of 6-months with
      Paricalcitol or standard treatment for hyperparathyroidism.

      After one month wash-out from any form of Vitamin D therapy, patients satisfying the
      inclusion/exclusion criteria will be randomized to two treatment arms:

        1. Paricalcitol capsules 1- 2 mcg/day/pts for 26 weeks

        2. Standard therapy for hyperparathyroidism for 26 weeks At the end of the first treatment
           period with Paricalcitol or Standard therapy each patient will cross-over to the other
           treatment.

      After baseline evaluation eligible patients will enter a 6 months treatment period whit oral
      paricalcitol (1-2 mcg/day), or standard treatment for hyperparathyroidism, added-on
      background therapy whit calcium and phosphate supplementation as deemed clinically
      appropriate.
    

Intervention name(s): Paricalcitol; Standard therapy
Intervention type(s): Drug; Drug
Intervention description(s): Paricalcitol capsules 1- 2 mcg/day/pts for 26 weeks; Standard therapy for hyperparathyroidism for 26 weeks
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Paricalcitol; Renal transplant; Secondary Hyperparathyroidism