A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.

NCT ID: NCT06481150

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2025-12-31

Brief Summary

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.

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.

Conditions

Hyperoxaluria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Tenapanor

30 mg Tenapanor twice a day

Group Type: EXPERIMENTAL

Tenapanor

Intervention Type: DRUG

Each tablet 30 mg

Placebo

30 mg Placebo twice a day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

Tenapanor

Each tablet 30 mg

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Other Intervention Names

XPHOZAH; IBSRELA

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Whittamore

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan M Whittamore, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jonathan M Whittamore, Ph.D.

Role: CONTACT

jonathan.whittamore@utsouthwestern.edu

2146489792

Sudeepa Bhattacharya

Role: CONTACT

Sudeepa.Bhattacharya@UTSouthwestern.edu

2146480324

Facility Contacts

Sudeepa Bhattacharya

Role: primary

sudeepa.bhattacharya@utsouthwestern.edu

2146480394

Miranda King

Role: backup

miranda.king@utsouthwestern.edu

2146482117

References

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.

Reference Type: BACKGROUND

PMID: 30158152 (View on PubMed)

Other Identifiers

1UL1TR003163

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU-2023-1257

Identifier Type: -

Identifier Source: org_study_id