Official Title: “Effect of Calcimimetic (Cinacalcet) on Phosphate-Induced Hyperparathyroidism in Children 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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Cinacalcet

Primary Measures

• The primary outcome will be the effect of cinacalcet on serum PTH.
  • Time Frame: PTH will be measured at time 0 and then every 30 minutes for 4 hours after receiving the medications
    

Secondary Measures

• Secondary outcome will be the effect of the calcimimetic on mineral homeostasis; ionized calcium, total calcium, and phosphate will be measured.
  • Time Frame: At time 0 and then every 30 minutes for 4 hours after receiving the medications
    

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 5 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Children's Mercy Hospital Kansas City

Overall Clinical Trial Officials and Contacts

Rachel Levy-Olomucki, MD Principal Investigator Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics  

Overall Contact: Rachel Levy-Olomucki, MD 816-234-3010 rlevy@cmh.edu

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00195936

Study ID Number: 05 02-027

ClinicalTrials.gov Identifier: NCT00195936

Health Authority: United States: Institutional Review Board