Calcitriol Monotherapy for X-Linked Hypophosphatemia

Early Phase 1

Recruiting

• Conditions: X-linked Hypophosphatemia; Hypophosphatemic Rickets, X-Linked Dominant; Hypophosphatemic Rickets
• Interventions: Drug: Calcitriol

• Registration Number: NCT03748966
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-11-19
• Study First Submitted QC: 2018-11-20
• Study First Posted: 2018-11-21
• Study Start: 2019-03-28
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-11
• Last Update Posted: 2024-03-12
• Primary Completion: 2025-03
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change from baseline in TmP/GFR in adults and children with XLH	up to 12 months	a measure of kidney resorption of phosphate
Change from baseline in serum phosphate in adults and children with XLH	up to 12 months
Change from baseline in nephrocalcinosis grade	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)
Rickets score for children with XLH	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)

Secondary Outcome Measures

Name	Time	Method
Growth in children with XLH	up to 12 months	Z-score of growth

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States