Calcitriol Monotherapy for X-Linked Hypophosphatemia

Study Overview
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Brief Summary
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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.

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

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

Intervention / Treatment
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* Drug: Calcitriol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adults with XLH<br>Adults with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year | Drug: Calcitriol<br>* 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.<br>* Other names: 1,25 dihydroxyvitamin D;|
| Experimental: Children with XLH<br>Children (age 3-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year | Drug: Calcitriol<br>* 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.<br>* Other names: 1,25 dihydroxyvitamin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in serum phosphate in adults and children with XLH |  | up to 12 months | 
| Change from baseline in TmP/GFR in adults and children with XLH | a measure of kidney resorption of phosphate | up to 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) | up to 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) | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth in children with XLH | Z-score of growth | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XLH, calcitriol, x-linked hypophosphatemia, rickets, 1,25 dihydroxyvitamin D, bone disorder, rare bone disease, vitamin D, hypophosphatemic rickets