HHRH, Hypercalciuria, Hypophosphatemia, Rickets, XLH
Conditions
Brief summary
Determine the association between duration and dose of chronic conventional therapy with Pi and renal (nephrocalcinosis/nephrolithiasis), vascular (endothelial function), and cardiovascular function (echo- cardiography) in patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and patients with X-linked hypophosphatemia (XLH).
Detailed description
The central hypothesis of this proposal is that patients with X-linked hypophosphatemia (XLH), when matched for duration and dose of phosphate (Pi) therapy to patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH), will evidence greater cardiovascular and vascular debility than patients with HHRH. The overall objectives of this project are to utilize our existing longitudinal databases for individuals with XLH and HHRH through an interdisciplinary collaboration between pediatric and adult endocrinology to: i) quantify the impact of exposure to Pi therapy across the lifespan on cardiovascular and renal complications, which are key aging endpoints, ii) determine the acute response to Pi loading in XLH and HHRH by studying the changes in surrogate markers of cardiovascular and renal function.
Interventions
DRUGphosphate
The target daily phosphate (Pi) intake is 3,500 mg/day (dietary intake plus our supplementation) for this study. Subjects will take a supplement of Pi (as KPhos Neutral 250 mg/tablet) to reach this target. Subjects will receive treatment for 30 days.
Sponsors
Yale University
National Center for Advancing Translational Sciences (NCATS)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
crossover parallel
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Children above the age of 13 years * Younger and older adults with XLH and HHRH with confirmed NPT2c mutations affecting both copies of the NPT2c gene (HHRH) or one copy of the PHEX gene (XLH) * Be willing to provide access to prior medical records to determine eligibility including imaging, biochemical, medical, and surgical history data * Be willing and able to complete all aspects of the study * Be willing to adhere to the study visit schedule and comply with the assessments (in the opinion of the investigator).
Exclusion criteria
* Subjects will be excluded, if they are children younger than age 13 years * Subjects that have other diseases likely to impact bone and mineral metabolism (e.g. renal, hepatic, gastrointestinal disorders, and malignancy), * Subjects that are currently pregnant, * Subjects that received medical therapy or developed any condition, which in the opinion of the investigator, could present a concern for either subject safety or difficulty with data interpretation. * Subjects will be excluded from Aim 2, if they are unable to tolerate supplemental phosphate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parathyroid Hormone (PTH) levels | 30 days | PTH levels are expected to increase over baseline after phosphate supplement (Pi). |
| Fibroblast Growth Factor 23 (FGF23) levels | 30 days | FGF23 levels are expected to increase over baseline after phosphate supplement (Pi). |
Countries
United States
Contacts
CONTACTClemens Bergwitz, MD
PRINCIPAL_INVESTIGATORClemens Bergwitz, MD
Yale University
Outcome results
None listed