The Impact of Phosphate Metabolism on Healthy Aging

Early Phase 1

Suspended

• Conditions: XLH; HHRH; Rickets; Hypercalciuria; Hypophosphatemia
• Interventions: Drug: phosphate

• Registration Number: NCT03771105
• Lead Sponsor: Yale University

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.

Study Timeline

• Study First Submitted: 2018-12-07
• Study First Submitted QC: 2018-12-07
• Study First Posted: 2018-12-10
• Study Start: 2019-01-01
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-13
• Last Update Posted: 2024-02-15
• Primary Completion: 2024-08
• Study Completion: 2024-08

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 30

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with X-linked Hypophosphatemia	phosphate	Patients with X-linked hypophosphatemia
15 Patients with X-linked Hypophosphatemia	phosphate	15 Patients with X-linked Hypophosphatemia that will receive phosphate treatment for 30 days.
15 Patients Hereditary hypophosphatemic rickets with HHRH	phosphate	15 patients withHereditary hypophosphatemic rickets with hypercalciuria (HHRH) that will receive phosphate treatment for 30 days.
Patients with hereditary hypophosphatemic rickets with HHRH	phosphate	Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)

Primary Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (1)

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States