Effect of Cinacalcet on Parathyroid Hormone Secretion in Children and Adolescents With Hypophosphatemic Rickets
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|ClinicalTrials.gov Identifier: NCT00195936|
Recruitment Status : Completed
First Posted : September 20, 2005
Last Update Posted : January 19, 2021
|Condition or disease||Intervention/treatment||Phase|
|Hypophosphatemic Rickets, X-Linked Dominant||Drug: Cinacalcet||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effect of Calcimimetic (Cinacalcet) on Phosphate-Induced Hyperparathyroidism in Children With Hypophosphatemic Rickets|
|Actual Study Start Date :||June 2005|
|Actual Primary Completion Date :||February 2008|
|Actual Study Completion Date :||February 2008|
Experimental: Overall Study
Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets
Single oral dose of Cinacalcet for children with Hypophosphatemic Rickets
- Change of serum Parathyroid Hormone (PTH) with use of cinacalcet [ Time Frame: Baseline, 30 minutes, and 4 hours post dose ]
- Change of mineral homeostasis; ionized calcium, total calcium, and phosphate with use of calcimimetic [ Time Frame: Baseline, 30 minutes, and 4 hours post dose ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00195936
|United States, Missouri|
|Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics|
|Kansas City, Missouri, United States, 64108|
|Principal Investigator:||Rachel Levy-Olomucki, MD||Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics|