The Impact of Phosphate Metabolism on Healthy Aging

Yale University

Status and phase: Suspended; Early Phase 1

Conditions: Rickets; XLH; Hypercalciuria; Hypophosphatemia; HHRH

Treatments: Drug: phosphate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03771105

1UL1TR001863-01 (U.S. NIH Grant/Contract)

2000023461

Details and patient eligibility

About

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).

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 4 patient groups

Patients with hereditary hypophosphatemic rickets with HHRH

Experimental group

Description:

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)

Treatment:

Drug: phosphate

Patients with X-linked Hypophosphatemia

Active Comparator group

Description:

Patients with X-linked hypophosphatemia

Treatment:

Drug: phosphate

15 Patients with X-linked Hypophosphatemia

Active Comparator group

Description:

15 Patients with X-linked Hypophosphatemia that will receive phosphate treatment for 30 days.

Treatment:

Drug: phosphate

15 Patients Hereditary hypophosphatemic rickets with HHRH

Active Comparator group

Description:

15 patients withHereditary hypophosphatemic rickets with hypercalciuria (HHRH) that will receive phosphate treatment for 30 days.

Treatment:

Drug: phosphate