Hypophosphatemic Rickets, Hypophosphatemic Rickets, X-Linked Dominant, X-linked Hypophosphatemia
Conditions
Keywords
XLH, calcitriol, x-linked hypophosphatemia, rickets, 1,25 dihydroxyvitamin D, bone disorder, rare bone disease, vitamin D, hypophosphatemic rickets
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.
Interventions
DRUGCalcitriol
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.
Sponsors
Massachusetts General Hospital
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
3 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphate in Adults and Children With XLH Between Baseline and 12 Months | baseline and 12 months | serum phosphate |
| Change From Baseline in TmP/GFR in Adults and Children With XLH | baseline and 12 months | a measure of kidney resorption of phosphate |
| Rickets Score for Children With XLH | baseline and 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 | baseline and 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
| Measure | Time frame | Description |
|---|---|---|
| Growth in Children With XLH | baseline and 12 months | Z-score of growth (this is full name of variable)- number represents standard deviation above or below the known mean of the general population at the corresponding age. Z score that is positive is above the mean, negative is below the mean. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREva Liu, MD
Massachusetts General Hospital and Brigham and Women's Hospital
Participant flow
Recruitment details
6 children with XLH were enrolled - Due to COVID and approval of burosumab, difficult to recruit children with XLH into trial 10 adults with XLH were enrolled
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 22.44 years STANDARD_DEVIATION 12.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 |
| other Total, other adverse events | 2 / 10 | 5 / 6 |
| serious Total, serious adverse events | 0 / 10 | 1 / 6 |
Outcome results
None listed