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

Phase 4
Conditions
X-linked Hypophosphatemia
Interventions
Registration Number
NCT03820518
Lead Sponsor
Peking Union Medical College Hospital
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
100
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High-doseCalcitriolReceiving 60 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.
Low-doseCalcitriolReceiving 20 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.
Primary Outcome Measures
NameTimeMethod
Change From Baseline to Post-treatment in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total ScoreBaseline, Month 12, 24

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

1. 2 condyles or plateaus

2. 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.

Secondary Outcome Measures
NameTimeMethod
Changes From Baseline to Post-treatment in Serum Total Alkaline Phosphatase (TALP) LevelsBaseline, Month 3, 6, 12, 18, 24

Changes From Baseline to Post-treatment in serum ALP

Changes From Baseline to Post-treatment in serum Carboxy-terminal Collagen Crosslinks (CTX) LevelsBaseline, Month 3, 6, 12, 18, 24

Changes From Baseline to Post-treatment in serum CTX

Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee ScoreBaseline, Month 12, 24

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

1. 2 condyles or plateaus

2. 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.

Changes From Baseline to Post-treatment in Growth VelocityBaseline, Month 12, 24

Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score

Changes From Baseline to Post-treatment in Serum Phosphorus LevelsBaseline, Month 3, 6, 12, 18, 24

Changes From Baseline to Post-treatment in Serum Phosphorus Levels

Changes From Baseline to Post-treatment in Severity of Dental AbscessBaseline, Month 3, 6, 12, 18, 24

The frequency and number of dental abscess will be collected by self-report and examed by investigators

Changes From Baseline to Post-treatment in Severity of Bone Pain as Measured by Visual Analog Pain ScalesBaseline, Month 3, 6, 12, 18, 24

Visual Analog Pain Scales (VAS) range from 0-10, and higher score represents severer pain

Changes From Baseline to Post-treatment in Severity of Leg DeformitiesBaseline, Month 3, 6, 12, 18, 24

The longest distance between two sides of thighs, knees, shanks and ankles are measured to evaluate the severity of leg deformities.

Changes From Baseline to Post-treatment in Serum Osteocalcin LevelsBaseline, Month 3, 6, 12, 18, 24

Changes From Baseline to Post-treatment in Serum Osteocalcin Levels

Changes From Baseline to Post-treatment in HeightBaseline, Month 3, 6, 12, 18, 24

Changes From Baseline to Post-treatment in Height

Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information SystemBaseline, 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

Trial Locations

Locations (1)

Department of Endocrinology, Peking Union Medical College Hospital

🇨🇳

Beijing, Beijing, China

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