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Trial record 1 of 1 for:    NCT03748966
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Calcitriol Monotherapy for X-Linked Hypophosphatemia

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ClinicalTrials.gov Identifier: NCT03748966
Recruitment Status : Recruiting
First Posted : November 21, 2018
Last Update Posted : August 13, 2019
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Eva Liu, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE November 19, 2018
First Posted Date  ICMJE November 21, 2018
Last Update Posted Date August 13, 2019
Actual Study Start Date  ICMJE March 28, 2019
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
  • Change from baseline in serum phosphate in adults and children with XLH [ Time Frame: up to 12 months ]
  • Change from baseline in TmP/GFR in adults and children with XLH [ Time Frame: up to 12 months ]
    a measure of kidney resorption of phosphate
  • Rickets score for children with XLH [ Time Frame: up to 12 months ]
    a score of rickets severity determined by reading x-rays of wrists and knees (10 point Thacher score with 0 being normal and 10 being severe)
  • Change from baseline in nephrocalcinosis grade [ Time Frame: up to 12 months ]
    determine if there is change in amount of calcifications in the kidneys: graded from grade 0 (normal) to grade IV (stone formation, solitary focus of echos at the tip of the renal pyramid)
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
  • Change from baseline in serum phosphate in adults and children with XLH [ Time Frame: up to 12 months ]
  • Change from baseline in TmP/GFR in adults and children with XLH [ Time Frame: up to 12 months ]
    a measure of kidney resorption of phosphate
  • Rickets score for children with XLH [ Time Frame: up to 12 months ]
    a score of rickets severity determined by reading x-rays of wrists and knees
  • Change from baseline in nephrocalcinosis grade [ Time Frame: up to 12 months ]
    determine if there is change in amount of calcifications in the kidneys
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
Growth in children with XLH [ Time Frame: up to 12 months ]
Z-score of growth
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Calcitriol Monotherapy for X-Linked Hypophosphatemia
Official Title  ICMJE Calcitriol Monotherapy for X-Linked Hypophosphatemia: Effects on Mineral Ions, Growth and Skeletal Parameters
Brief Summary Children and adults with XLH recruited will be treated with calcitriol alone (without phosphate supplementation) for one year, during which the calcitriol dose will be escalated during the first 3 months of therapy. The investigators hypothesize that treatment of adults and children with XLH alone will improve serum phosphate levels and skeletal mineralization without causing an increase in kidney calcifications. The study will also examine if calcitriol therapy will improve growth in children.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Adults or children (age 6-17) with X-linked hypophosphatemia (XLH) will be enrolled the study. All research subjects will be treated with optimized doses of calcitriol alone (without phosphate supplementation) for one year.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • X-linked Hypophosphatemia
  • Hypophosphatemic Rickets
  • Hypophosphatemic Rickets, X-Linked Dominant
Intervention  ICMJE Drug: Calcitriol
Adults and children (age 6-17) with X-linked hypophosphatemia will be treated with calcitriol therapy without phosphate supplementation. Doses of calcitriol will be escalated and optimized in the first three months of the study. Calcitriol is an oral medication taken once a day.
Other Name: 1,25 dihydroxyvitamin D
Study Arms  ICMJE
  • Experimental: Adults with XLH
    Adults with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year
    Intervention: Drug: Calcitriol
  • Experimental: Children with XLH
    Children (age 6-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year
    Intervention: Drug: Calcitriol
Publications * Liu ES, Martins JS, Raimann A, Chae BT, Brooks DJ, Jorgetti V, Bouxsein ML, Demay MB. 1,25-Dihydroxyvitamin D Alone Improves Skeletal Growth, Microarchitecture, and Strength in a Murine Model of XLH, Despite Enhanced FGF23 Expression. J Bone Miner Res. 2016 May;31(5):929-39. doi: 10.1002/jbmr.2783. Epub 2016 Feb 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Clinical diagnosis of XLH with family history excluding male-to-male transmission, or positive genotype for PHEX mutation
  • Serum PTH levels less than 1.5x the upper limit of normal
  • Serum calcium levels less than 10.0 mg/dl
  • eGFR >= 60 mL/min/1.73m2
  • 25(OH) vitamin D level >= 20 ng/dL

Exclusion Criteria:

  • Known allergy to calcitriol
  • Pregnancy or breast feeding
  • Use of skeletally active agents such as bisphosphonates, teriparatide, SERMS, hormone replacement therapy and progesterone-only contraceptive agents (combination oral contraceptive use in premenopausal women is not an exclusion criterion).
  • Unwilling or unable to stop therapy with calcitriol and phosphate therapy for two weeks prior to study
  • Therapy with cinacalcet within the past two weeks
  • Current use of growth hormone therapy
  • Use of diuretics or medications that alter renal handling of mineral ions.
  • Use of glucocorticoids for more than 14 days in the past 12 months with the exception of inhaled agents.
  • History of malignancy except basal and squamous cell carcinoma of the skin.
  • Significant history of psychiatric disease per DSM-5.
  • Substance use disorder per DSM-5.
  • Significant cardiopulmonary disease (unstable CAD or stage D ACC/AHA heart failure).
  • Absence of laboratory values for serum calcium, phosphate and creatinine in the 24 months prior to enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eva S Liu, MD 16175255412 esliu@bwh.harvard.edu
Contact: Marie Demay, MD 16177263273 demay@helix.mgh.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03748966
Other Study ID Numbers  ICMJE 2016P001000
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Eva Liu, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators  ICMJE
Principal Investigator: Eva Liu, MD Massachusetts General Hospital and Brigham and Women's Hospital
PRS Account Massachusetts General Hospital
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP