Clinical trial NCT03748966: Calcitriol Monotherapy for X-Linked Hypophosphatemia
Official title: Calcitriol Monotherapy for X-Linked Hypophosphatemia: Effects on Mineral Ions, Growth and Skeletal Parameters
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: X-linked Hypophosphatemia
Hypophosphatemic Rickets
Hypophosphatemic Rickets, X-Linked Dominant
Keywords: XLH
calcitriol
x-linked hypophosphatemia
rickets
1,25 dihydroxyvitamin D
bone disorder
rare bone disease
vitamin D
hypophosphatemic rickets
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2018-11-21
Enrollment: 20
Sex: ALL
Minimum age (years): 3
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in serum phosphate in adults and children with XLH
timeFrame: up to 12 months
measure: Change from baseline in TmP/GFR in adults and children with XLH
timeFrame: up to 12 months
measure: Rickets score for children with XLH
timeFrame: up to 12 months
measure: Change from baseline in nephrocalcinosis grade
timeFrame: up to 12 months
Secondary outcomes:
measure: Growth in children with XLH
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital and Brigham and Women's Hospital
name: Eva Liu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.