A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.

This pilot study is proposing a novel approach to directly target intestinal oxalate absorption with the drug Tenapanor, which was recently FDA-approved for treating hyperphosphatemia in patients with chronic kidney disease. Tenapanor works by blocking paracellular phosphate absorption by the intestine, but the underlying mechanisms have not been clearly defined. Since phosphate and oxalate ions are absorbed through the same paracellular pathway, and are of similar size and charge, Tenapanor is hypothesized to also reduce dietary oxalate absorption and consequently lower urinary oxalate excretion.

Study Overview

• Status: Completed
• Conditions: Hyperoxaluria
• Intervention / Treatment: Other: Placebo; Drug: Tenapanor

Detailed Description

The proposed proof-of-concept studies will determine whether Tenapanor reduces urine oxalate in normal human subjects receiving a high-oxalate diet in a crossover placebo-controlled short-term metabolic study.

Study Design Screening - One 24-hour urine for analysis of stone-risk profile, one blood sample for comprehensive metabolic panel and cystatin C, one stool sample for fecal calprotectin, physical exam, social and medical history, vital signs, demographic information, personal information.This is a two-phase study, each phase is 5 days in duration.

Phase 1: The subjects will consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day just prior to the morning and evening meals. On days 4 and 5 they will collect two 24-hour urines for measurement of urine oxalate and stone-risk profile.

Washout: The subjects will undergo a 9-day washout period. Phase 2: The subjects will consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day just prior to the morning and evening meals. On days 4 and 5 they will collect two 24-hour urines for measurement of urine oxalate and stone-risk profile.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Normal, healthy adult volunteers

Exclusion Criteria:

• Personal history of kidney stones
• Pregnant or nursing
• Recurrent urinary tract infections
• Lithogenic urine chemistry at baseline (oxalate > 45 mg/24 h, urine calcium > 300 mg/24 h)
• Chronic kidney disease (eGFR < 90 mL/min/1.73m2)
• Personal history of GI disease, GI obstruction, or GI surgery
• Chronic diarrhea
• Intestinal inflammation (Fecal calprotectin > 120 mcg/g)
• Drugs which are substrates of OATP2B1 (e.g. enalapril)
• Chronic use of sodium polystyrene sulfonate, angiotensin-converting enzyme inhibitors, diuretics, antacids, alkali treatment, or carbonic anhydrase inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenapanor; 30 mg Tenapanor twice a day	Drug: Tenapanor; Each tablet 30 mg; Other Names: IBSRELA; XPHOZAH
Placebo Comparator: Placebo; 30 mg Placebo twice a day	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-h urine oxalate	Study participants collect two 24-hour urine specimens for analysis of their stone-risk profile, including oxalate (mg/24 h), comparing placebo with drug treatment (Tenapanor).	Two 24-h urine on days 4 and 5 of each arm

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Jonathan M Whittamore, Ph.D., University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• King AJ, Siegel M, He Y, Nie B, Wang J, Koo-McCoy S, Minassian NA, Jafri Q, Pan D, Kohler J, Kumaraswamy P, Kozuka K, Lewis JG, Dragoli D, Rosenbaum DP, O'Neill D, Plain A, Greasley PJ, Jonsson-Rylander AC, Karlsson D, Behrendt M, Stromstedt M, Ryden-Bergsten T, Knopfel T, Pastor Arroyo EM, Hernando N, Marks J, Donowitz M, Wagner CA, Alexander RT, Caldwell JS. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci Transl Med. 2018 Aug 29;10(456):eaam6474. doi: 10.1126/scitranslmed.aam6474.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Actual): September 14, 2025
• Study Completion (Actual): September 14, 2025

Study Registration Dates

• First Submitted: June 24, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Hyperoxaluria; tenapanor
• Other Study ID Numbers: STU-2023-1257; 1UL1TR003163 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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