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

Study Overview
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Brief Summary
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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.

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

Conditions
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X-linked Hypophosphatemia

Intervention / Treatment
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* Drug: Calcitriol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |