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

NCT ID: NCT00195936

Last Updated: 2021-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2008-02-29

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.

Conditions

Hypophosphatemic Rickets, X-Linked Dominant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Overall Study

Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets

Group Type: EXPERIMENTAL

Cinacalcet

Intervention Type: DRUG

Single oral dose of Cinacalcet for children with Hypophosphatemic Rickets

Interventions

Cinacalcet

Single oral dose of Cinacalcet for children with Hypophosphatemic Rickets

Intervention Type: DRUG

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

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Mercy Hospital Kansas City

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rachel Levy-Olomucki, MD

Role: PRINCIPAL_INVESTIGATOR

Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics

Locations

Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Countries

United States

Other Identifiers

05 02-027

Identifier Type: -

Identifier Source: org_study_id