Calcitriol Monotherapy for X-Linked Hypophosphatemia

X-linked Hypophosphatemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03748966
• Other study ID #: 2016P001000
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 28, 2019
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: Massachusetts General Hospital
• Contact: Eva S Liu, MD
• Phone: 16175255412
• Email: esliu[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypophosphatemic Rickets
• Hypophosphatemia
• Hypophosphatemic Rickets
• Hypophosphatemic Rickets, X-Linked Dominant
• Rickets
• X-linked Hypophosphatemia

Intervention

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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in serum phosphate in adults and children with XLH		up to 12 months
Primary	Change from baseline in TmP/GFR in adults and children with XLH	a measure of kidney resorption of phosphate	up to 12 months
Primary	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)	up to 12 months
Primary	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)	up to 12 months
Secondary	Growth in children with XLH	Z-score of growth	up to 12 months