The Impact of Phosphate Metabolism on Healthy Aging

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).

Study Overview

• Status: Recruiting
• Conditions: Rickets; Hypophosphatemia; Hypercalciuria; XLH; HHRH
• Intervention / Treatment: Drug: phosphate

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Clemens Bergwitz, MD; Phone Number: 203-737-5450; Email: clemens.bergwitz@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale University School Of Medicine
      • Contact: Clemens Bergwitz, M.D.; Phone Number: 203-737-5450; Email: clemens.bergwitz@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with hereditary hypophosphatemic rickets with HHRH; Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)	Drug: phosphate; 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.
Active Comparator: Patients with X-linked Hypophosphatemia; Patients with X-linked hypophosphatemia	Drug: phosphate; 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.
Active Comparator: 15 Patients with X-linked Hypophosphatemia; 15 Patients with X-linked Hypophosphatemia that will receive phosphate treatment for 30 days.	Drug: phosphate; 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.
Active Comparator: 15 Patients Hereditary hypophosphatemic rickets with HHRH; 15 patients withHereditary hypophosphatemic rickets with hypercalciuria (HHRH) that will receive phosphate treatment for 30 days.	Drug: phosphate; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parathyroid Hormone (PTH) levels	PTH levels are expected to increase over baseline after phosphate supplement (Pi).	30 days
Fibroblast Growth Factor 23 (FGF23) levels	FGF23 levels are expected to increase over baseline after phosphate supplement (Pi).	30 days

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Clemens Bergwitz, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 7, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Nutrition Disorders; Metabolic Diseases; Urological Manifestations; Bone Diseases, Metabolic; Phosphorus Metabolism Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Calcium Metabolism Disorders; Vitamin D Deficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Hypophosphatemia; Rickets; Hypercalciuria; Inorganic Chemicals; Anions; Ions; Electrolytes; Acids, Noncarboxylic; Acids; Phosphoric Acids; Phosphorus Acids; Phosphorus Compounds; Phosphates
• Other Study ID Numbers: 2000023461; 1UL1TR001863-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes