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

January 15, 2021 updated by: Children's Mercy Hospital Kansas City

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Section of Pediatric Nephrology, Children's Mercy Hospitals and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Overall Study
Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets
Drug: Cinacalcet
Single oral dose of Cinacalcet for children with Hypophosphatemic Rickets

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Mercy Hospital Kansas City

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 1, 2005

Primary Completion (ACTUAL)

February 1, 2008

Study Completion (ACTUAL)

February 1, 2008

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (ESTIMATE)

September 20, 2005

Study Record Updates

Last Update Posted (ACTUAL)

January 19, 2021

Last Update Submitted That Met QC Criteria

January 15, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05 02-027

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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