Using Different Doses of Active Vitamin D Combined With Neutral Phosphate in Children With X-linked Hypophosphatemia

Comparing the Effectiveness of High or Low Dose of Active Vitamin D Combined With Neutral Phosphate in Children With X-linked Hypophosphatemia

X-linked hypophosphatemia (XLH) is the most common form of heritable rickets. Current treatments include active vitamin D metabolites (e.g. calcitriol) and phosphate salts. There is no consistent weight-based dosing of calcitriol and phosphate now. The primary objective of this study is to establish the efficacy of different dose of calcitriol combined with neutral phosphate in children with XLH.

Study Overview

• Status: Unknown
• Conditions: X-linked Hypophosphatemia
• Intervention / Treatment: Drug: Calcitriol

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Weibo Xia, MD; Phone Number: +86 13501002126; Email: xiaweibo8301@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Department of Endocrinology, Peking Union Medical College Hospital
      • Contact: Weibo Xia, MD; Phone Number: +86 13501002126; Email: xiaweibo8301@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, aged 1-12 years, inclusive
• Diagnosis of XLH by clinical features: serum phosphorus level < 2.5 mg/dl; ALP?; RSS total score ≥2; bowed legs; short stature; family history with appropriate X-linked inheritance
• Meet at least one of the following: confirmed Phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX) mutation in the participant, or serum FGF23 level >30 pg/ml (Kainos assay)
• Willing to participate the study, and provide an informed consent
• Able to complete all aspects of study and adhere to the visit schedule

Exclusion Criteria:

• Use of growth hormone within 12 months before first visit
• Height >50 percentile for age and sex specific data
• Presence of nephrocalcinosis or nephrolithiasis
• Serum intact parathyroid hormone level>170 pg/ml
• Plan to receive orthopaedic surgery in 12 months
• Poor compliance
• Use of gonadotropin-releasing hormone therapy right now
• Use of aluminium hydroxide, steroid, acetazolamide or thiazide drugs within 7 days before first visit
• Not be fit to participant in the study, by the judgement of investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose; Receiving 60 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.	Drug: Calcitriol; Other Names: Elementary phosphorus
Experimental: Low-dose; Receiving 20 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.	Drug: Calcitriol; Other Names: Elementary phosphorus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Post-treatment in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total Score	RSS range from 0 to 10, and higher RSS represent severer rickets. It is consisted of score of worst wrist (0-4) and worst knee (0-6). WRIST-score both radius and ulna separately-2 bones × 2 points = 4 points possible KNEE-score both femur and tibia separately Multiply the grade in A by the multiplier in B for each bone, then add femur and tibia scores together A: Grade 1 2 3 B: Multiplier Portion of growth plate affected 0.5 ≤ 1 condyle or plateau; 2 condyles or plateaus; bones × 1 point × 3 points = 6 points possible Total: 10 points possible Reference:Thacher, T. Radiographic scoring method for the assessment of the severity of nutritional rickets[J]. Journal of Tropical Pediatrics, 2000, 46(3):132-139.	Baseline, Month 12, 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score	RSS range from 0 to 10, and higher RSS represent severer rickets. It is consisted of score of worst wrist (0-4) and worst knee (0-6). WRIST-score both radius and ulna separately-2 bones × 2 points = 4 points possible KNEE-score both femur and tibia separately Multiply the grade in A by the multiplier in B for each bone, then add femur and tibia scores together A: Grade 1 2 3 B: Multiplier Portion of growth plate affected 0.5 ≤ 1 condyle or plateau; 2 condyles or plateaus; bones × 1 point × 3 points = 6 points possible Total: 10 points possible Reference:Thacher, T. Radiographic scoring method for the assessment of the severity of nutritional rickets[J]. Journal of Tropical Pediatrics, 2000, 46(3):132-139.	Baseline, Month 12, 24
Changes From Baseline to Post-treatment in Growth Velocity	Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score	Baseline, Month 12, 24
Changes From Baseline to Post-treatment in Serum Total Alkaline Phosphatase (TALP) Levels	Changes From Baseline to Post-treatment in serum ALP	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in serum Carboxy-terminal Collagen Crosslinks (CTX) Levels	Changes From Baseline to Post-treatment in serum CTX	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in Serum Phosphorus Levels	Changes From Baseline to Post-treatment in Serum Phosphorus Levels	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in Severity of Dental Abscess	The frequency and number of dental abscess will be collected by self-report and examed by investigators	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in Severity of Bone Pain as Measured by Visual Analog Pain Scales	Visual Analog Pain Scales (VAS) range from 0-10, and higher score represents severer pain	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in Severity of Leg Deformities	The longest distance between two sides of thighs, knees, shanks and ankles are measured to evaluate the severity of leg deformities.	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in Serum Osteocalcin Levels	Changes From Baseline to Post-treatment in Serum Osteocalcin Levels	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in Height	Changes From Baseline to Post-treatment in Height	Baseline, Month 3, 6, 12, 18, 24
Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information System	Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information System	Baseline, Month 3, 6, 12, 18, 24

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: January 25, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 28, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Metabolism, Inborn Errors; Bone Diseases, Metabolic; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Metal Metabolism, Inborn Errors; Phosphorus Metabolism Disorders; Rickets; Vitamin D Deficiency; Rickets, Hypophosphatemic; Hypophosphatemia, Familial; Familial Hypophosphatemic Rickets; Hypophosphatemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Calcitriol
• Other Study ID Numbers: JS-1824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No