Effect of Cinacalcet on Parathyroid Hormone Secretion in Children and Adolescents With Hypophosphatemic Rickets

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Calcimimetic (Cinacalcet) on Phosphate-Induced Hyperparathyroidism in Children With Hypophosphatemic Rickets

Conditions
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Hypophosphatemic Rickets, X-Linked Dominant

Intervention / Treatment
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* Drug: Cinacalcet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Overall Study<br>Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets | Drug: Cinacalcet<br>* Single oral dose of Cinacalcet for children with Hypophosphatemic Rickets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of serum Parathyroid Hormone (PTH) with use of cinacalcet |  | Baseline, 30 minutes, and 4 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of mineral homeostasis; ionized calcium, total calcium, and phosphate with use of calcimimetic |  | Baseline, 30 minutes, and 4 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cinacalcet, PTH, XLH, children and adolescents with hypophosphatemic rickets (XLH)