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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

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.

Condition or disease Intervention/treatment Phase
X-linked Hypophosphatemia Hypophosphatemic Rickets Hypophosphatemic Rickets, X-Linked Dominant Drug: Calcitriol Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
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
Official Title: Calcitriol Monotherapy for X-Linked Hypophosphatemia: Effects on Mineral Ions, Growth and Skeletal Parameters
Actual Study Start Date : March 28, 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Experimental: Adults with XLH
Adults with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year
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

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
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




Primary Outcome Measures :
  1. Change from baseline in serum phosphate in adults and children with XLH [ Time Frame: up to 12 months ]
  2. 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

  3. 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)

  4. 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)


Secondary Outcome Measures :
  1. Growth in children with XLH [ Time Frame: up to 12 months ]
    Z-score of growth



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Ages Eligible for Study:   6 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03748966


Contacts
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Contact: Eva S Liu, MD 16175255412 esliu@bwh.harvard.edu
Contact: Marie Demay, MD 16177263273 demay@helix.mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Eva Liu, MD    617-525-5412    esliu@bwh.harvard.edu   
Contact: Marie Demay, MD    6177263273    demay@helix.mgh.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
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Principal Investigator: Eva Liu, MD Massachusetts General Hospital and Brigham and Women's Hospital

Publications:
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Responsible Party: Eva Liu, Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03748966     History of Changes
Other Study ID Numbers: 2016P001000
First Posted: November 21, 2018    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Eva Liu, Massachusetts General Hospital:
XLH
calcitriol
x-linked hypophosphatemia
rickets
1,25 dihydroxyvitamin D
bone disorder
rare bone disease
vitamin D
hypophosphatemic rickets
Additional relevant MeSH terms:
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Calcitriol
Rickets
Familial Hypophosphatemic Rickets
Rickets, Hypophosphatemic
Hypophosphatemia
Phosphorus Metabolism Disorders
Metabolic Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium Metabolism Disorders
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Dihydroxycholecalciferols
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents