Calcitriol Monotherapy for X-Linked Hypophosphatemia

Calcitriol Monotherapy for X-Linked Hypophosphatemia: Effects on Mineral Ions, Growth and Skeletal Parameters

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.

Study Overview

• Status: Completed
• Conditions: X-linked Hypophosphatemia; Hypophosphatemic Rickets; Hypophosphatemic Rickets, X-Linked Dominant
• Intervention / Treatment: Drug: Calcitriol

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 3-17) 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 Names: 1,25 dihydroxyvitamin D
Experimental: Children with XLH; Children (age 3-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year	Drug: Calcitriol; Adults and children (age 3-17) 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 Names: 1,25 dihydroxyvitamin D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Phosphate in Adults and Children With XLH Between Baseline and 12 Months	serum phosphate	baseline and 12 months
Change From Baseline in TmP/GFR in Adults and Children With XLH	a measure of kidney resorption of phosphate	baseline and 12 months
Rickets Score for Children With XLH	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)	baseline and 12 months
Change From Baseline in Nephrocalcinosis Grade	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)	baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth in Children With XLH	Z-score of growth (this is full name of variable)- number represents standard deviation above or below the known mean of the general population at the corresponding age. Z score that is positive is above the mean, negative is below the mean.	baseline and 12 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Eva Liu, MD, Massachusetts General Hospital and Brigham and Women's Hospital

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Actual): March 1, 2025
• Study Completion (Actual): February 26, 2026

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: vitamin D; XLH; rickets; calcitriol; hypophosphatemic rickets; x-linked hypophosphatemia; 1,25 dihydroxyvitamin D; bone disorder; rare bone disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Musculoskeletal Diseases; Nutrition Disorders; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Bone Diseases, Metabolic; Phosphorus Metabolism Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Metal Metabolism, Inborn Errors; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Vitamin D Deficiency; Hypophosphatemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Familial Hypophosphatemic Rickets; Bone Diseases; Rickets; Rickets, Hypophosphatemic; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Hydroxycholecalciferols; Cholecalciferol; Dihydroxycholecalciferols; Calcitriol; 1,25-dihydroxyvitamin D
• Other Study ID Numbers: 2016P001000

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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