Calcitriol Monotherapy for X-Linked Hypophosphatemia

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03748966

Collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH)

Enrollment

Location

Arms

59.1

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 28, 2019

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

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 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. Other Names: 1,25 dihydroxyvitamin D
Experimental: Children with XLH Children (age 3-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year	Drug: Calcitriol Adults and children (age 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. Other Names: 1,25 dihydroxyvitamin D

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 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.

Other Names:

1,25 dihydroxyvitamin D

Experimental: Children with XLH

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

Drug: Calcitriol

Other Names:

1,25 dihydroxyvitamin D

Outcome Measures

Primary Outcome Measures

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 [up to 12 months]
a measure of kidney resorption of phosphate
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)
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)

Secondary Outcome Measures

Growth in children with XLH [up to 12 months]
Z-score of growth

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.