Clinical trial NCT00195936: Effect of Cinacalcet on Parathyroid Hormone Secretion in Children and Adolescents With Hypophosphatemic Rickets
Official title: Effect of Calcimimetic (Cinacalcet) on Phosphate-Induced Hyperparathyroidism in Children With Hypophosphatemic Rickets
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypophosphatemic Rickets, X-Linked Dominant
Keywords: Cinacalcet
PTH
XLH
children and adolescents with hypophosphatemic rickets (XLH)
Lead sponsor: Children's Mercy Hospital Kansas City
Sponsor class: OTHER
First posted: 2005-09-20
Enrollment: 8
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of serum Parathyroid Hormone (PTH) with use of cinacalcet
timeFrame: Baseline, 30 minutes, and 4 hours post dose
Secondary outcomes:
measure: Change of mineral homeostasis; ionized calcium, total calcium, and phosphate with use of calcimimetic
timeFrame: Baseline, 30 minutes, and 4 hours post dose
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics
state: Missouri
Study officials:
affiliation: Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics
name: Rachel Levy-Olomucki, MD
role: PRINCIPAL_INVESTIGATOR
References: