Effect of Cinacalcet on Parathyroid Hormone Secretion in Children and Adolescents With Hypophosphatemic Rickets
Effect of Cinacalcet on Parathyroid Hormone Secretion in Children and Adolescents With Hypophosphatemic Rickets
This study will measure the effect of cinacalcet (Sensipar) on parathyroid hormone (PTH)
 secretion in children and adolescents with hypophosphatemic rickets (XLH). The investigators
 are seeking evidence that patients with XLH may benefit from treatment with cinacalcet by
 achieving better control of PTH secretion.
X-linked hypophosphatemic rickets (XLH) is an X-linked dominant genetic disorder. Common
 findings are low serum phosphate and inadequate 1,25(OH)2 vitamin D production. It is
 generally believed that the primary defect in XLH is impaired renal tubular transport of
 phosphate coupled with abnormal regulation of the enzyme responsible for the 1-alfa
 hydroxylation of 25(OH) vitamin D. The current treatment of children with XLH is large oral
 doses of phosphate and 1,25-dihydroxyvitamin D. There are two common side effects to this
 treatment; nephrocalcinosis and secondary hyperparathyroidism (HPT). The latter at times may
 cause hypertension, hypercalcemia, and permanent renal damage. The complication of secondary
 hyperparathyroidism is seen in 20% of the patients. The release of PTH from the glands into
 the circulation is tightly regulated by serum calcium concentration. The glands "read" serum
 calcium concentration via Ca sensing receptors (CaR) which are located at the surface of the
 glands. Calcimimetics are compounds that allosterically modulate the CaR, thereby enhancing
 its sensitivity to circulating serum calcium concentrations and consequently decreasing PTH
 secretion. When used in primary HPT, they rapidly reduce PTH level and normalize serum
 calcium concentration.

 Cinacalcet is a calcimimetic agent recently approved by the FDA for treating hypercalcemia in
 patients with parathyroid carcinoma and secondary HPT in patients with chronic renal disease.
 Cinacalcet was found to be effective in decreasing both PTH level and the calcium X
 phosphorous ion product in dialysis patients.

 The goal of our proposed acute study is to see whether concomitant administration of
 Cinacalcet and phosphate, to patients with XLH, will block completely or partially secretion
 of PTH (day 2), expected to be seen following administration of phosphate alone (day 1). We
 will also monitor serum phosphate, total calcium, and ionized calcium concentration to learn
 to what extent, if any, blockage of PTH secretion affects mineral homeostasis under this
 condition.

 If found to be effective in blocking PTH secretion, Cinacalcet will become a candidate for a
 long-term study in children with XLH to protect them from developing secondary
 hyperparathyroidism.
Inclusion Criteria:

 -  Established patients with XLH

 -  Age 5 years old and above

 -  Normal serum calcium and creatinine concentrations

 Exclusion Criteria:

 -  Patients with hypersensitivity to any component(s) of cinacalcet

 -  Hypocalcaemia

 -  Elevated serum creatinine