Calcitriol Monotherapy for X-Linked Hypophosphatemia

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

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

Contact: Eva S Liu, MD; 16175255412; esliu@bwh.harvard.edu

Contact: Marie Demay, MD; 16177263273; demay@helix.mgh.harvard.edu

Locations

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

• Principal Investigator: Eva Liu, MD; Massachusetts General Hospital and Brigham and Women's Hospital

More Information

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.

• Responsible Party: Eva Liu, Assistant Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03748966
• Other Study ID Numbers: 2016P001000
• First Posted: November 21, 2018
• Last Update Posted: August 13, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

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; Calcitriol; Dihydroxycholecalciferols; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Calcium Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents