Calcitriol Monotherapy for X-Linked Hypophosphatemia

NCT03748966 | Completed Early Phase 1 Results DMC FDA Drug

• 1 other identifier: 2016P001000
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

X-linked Hypophosphatemia; Hypophosphatemic Rickets; Hypophosphatemic Rickets, X-Linked Dominant

Keywords

XLH; calcitriol; x-linked hypophosphatemia; rickets; 1,25 dihydroxyvitamin D; bone disorder; rare bone disease; vitamin D; hypophosphatemic rickets

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Growth in Children With XLH

  baseline and 12 months

Study Arms (2)

Adults with XLH

EXPERIMENTAL

Adults with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year

Drug: Calcitriol

Children with XLH

EXPERIMENTAL

Children (age 3-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year

Drug: Calcitriol

Interventions

Calcitriol DRUG

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.

Also known as: 1,25 dihydroxyvitamin D

Adults with XLH; Children with XLH

Eligibility Criteria

• Age: 3 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• (OH) vitamin D level \>= 20 ng/dL

You may not qualify if:

• Known allergy to calcitriol
• Pregnancy or breast feeding
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 26751835 BACKGROUND

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets; Rickets, Hypophosphatemic; Rickets; Bone Diseases

Interventions

Calcitriol; 1,25-dihydroxyvitamin D

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Musculoskeletal Diseases; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Hypophosphatemia; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: Eva Liu
• Organization: Mass General Brigham

esliu@bwh.harvard.edu

6175255412

Study Officials

• Eva Liu, MD

  Massachusetts General Hospital and Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Adults or children (age 3-17) 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.

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 21, 2018
• Study Start: March 28, 2019
• Primary Completion: March 1, 2025
• Study Completion: February 26, 2026
• Last Updated: May 7, 2026
• Results First Posted: May 7, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)