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

• ClinicalTrials.gov Identifier: NCT03820518
• Recruitment Status: Recruiting
• First Posted: January 29, 2019
• Last Update Posted: January 30, 2019
• Sponsor: Peking Union Medical College Hospital
• Information provided by (Responsible Party): Peking Union Medical College Hospital

Tracking Information

• First Submitted Date: January 25, 2019
• First Posted Date: January 29, 2019
• Last Update Posted Date: January 30, 2019
• Actual Study Start Date: January 1, 2017
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 28, 2019)

Change From Baseline to Post-treatment in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total Score [ Time Frame: Baseline, 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.

Original Primary Outcome Measures (submitted: January 25, 2019)

Change From Baseline to Post-treatment in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total Score [ Time Frame: Baseline, Month 12, 24 ]

Change From Baseline to Post-treatment in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total Score

Current Secondary Outcome Measures (submitted: January 28, 2019)

• Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score [ Time Frame: Baseline, 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 Velocity [ Time Frame: Baseline, 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 Total Alkaline Phosphatase (TALP) Levels [ Time Frame: Baseline, 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) Levels [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in serum CTX
• Changes From Baseline to Post-treatment in Serum Phosphorus Levels [ Time Frame: Baseline, 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 Abscess [ Time Frame: Baseline, 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 Scales [ Time Frame: Baseline, 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 Deformities [ Time Frame: Baseline, 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 Levels [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Serum Osteocalcin Levels
• Changes From Baseline to Post-treatment in Height [ Time Frame: Baseline, 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 System [ Time Frame: 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

Original Secondary Outcome Measures (submitted: January 25, 2019)

• Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score [ Time Frame: Baseline, 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 Growth Velocity [ Time Frame: Baseline, 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 Alkaline Phosphatase [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Alkaline Phosphatase
• Changes From Baseline to Post-treatment in Carboxy-terminal Collagen Crosslinks [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Carboxy-terminal Collagen Crosslinks
• Changes From Baseline to Post-treatment in Serum Phosphorus Levels [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Carboxy-terminal Collagen Crosslinks
• Changes From Baseline to Post-treatment in Severity of Dental Abscess [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Carboxy-terminal Collagen Crosslinks
• Changes From Baseline to Post-treatment in Severity of Bone Pain as Measured by Visual Analog Pain Scales [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Carboxy-terminal Collagen Crosslinks
• Changes From Baseline to Post-treatment in Severity of Leg Deformities [ Time Frame: Baseline, 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 Osteocalcin [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Osteocalcin
• Changes From Baseline to Post-treatment in Height Z Score [ Time Frame: Baseline, Month 3, 6, 12, 18, 24 ]
  Changes From Baseline to Post-treatment in Height Z Score
• Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information System [ Time Frame: 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Using Different Doses of Active Vitamin D Combined With Neutral Phosphate in Children With X-linked Hypophosphatemia
• Official Title: Comparing the Effectiveness of High or Low Dose of Active Vitamin D Combined With Neutral Phosphate in Children With X-linked Hypophosphatemia
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: X-linked Hypophosphatemia

Intervention

Drug: Calcitriol

Other Name: Elementary phosphorus

Study Arms

• Experimental: High-dose
  Receiving 60 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.
  Intervention: Drug: Calcitriol
• Experimental: Low-dose
  Receiving 20 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.
  Intervention: Drug: Calcitriol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 25, 2019): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 12 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Weibo Xia, MD; +86 13501002126; xiaweibo8301@163.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03820518
• Other Study ID Numbers: JS-1824
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Peking Union Medical College Hospital
• Study Sponsor: Peking Union Medical College Hospital
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Peking Union Medical College Hospital
• Verification Date: January 2019