Calcitriol Monotherapy for X-Linked Hypophosphatemia

Purpose

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.

Conditions

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

Eligibility

Eligible Ages
Between 3 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Phase
Early Phase 1
Study Type
Interventional
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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Eva Liu, MD
617-525-5412
esliu@bwh.harvard.edu

More Details

Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

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