Tenapanor for Kidney Stones

Recruiting in Palo Alto (17 mi)

Overseen by Jonathan M Whittamore, Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: OATP2B1 substrates, ACE inhibitors

Disqualifiers: Kidney stones, Pregnancy, GI disease, others

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially if you use drugs like enalapril or others listed in the exclusion criteria. It's best to discuss your current medications with the trial team to see if any changes are needed.

What makes the drug Tenapanor unique for treating kidney stones?

Tenapanor is unique because it works by reducing the absorption of sodium in the intestines, which can help manage conditions like kidney stones by potentially altering the mineral balance in the body. This mechanism is different from traditional treatments that often focus on breaking down or removing existing stones. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with high urinary oxalate levels (hyperoxaluria) and those at risk of kidney stones. Participants should be adults who have not been diagnosed with chronic kidney disease but are experiencing these conditions.

Inclusion Criteria

I am a healthy adult.

Exclusion Criteria

Pregnant or nursing

My kidney function is reduced.

Lithogenic urine chemistry at baseline (oxalate > 45 mg/24 h, urine calcium > 300 mg/24 h)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Phase 1 Treatment

Participants consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day. Urine samples are collected on days 4 and 5.

5 days

Daily visits for monitoring

Washout

Participants undergo a 9-day washout period between treatment phases.

9 days

Phase 2 Treatment

Participants consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day. Urine samples are collected on days 4 and 5.

5 days

Daily visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Tenapanor (Other)

Trial Overview The study tests Tenapanor, a drug approved for another kidney condition, to see if it can also reduce the absorption of oxalate from food and lower the risk of kidney stones. A placebo group will serve as a comparison to measure Tenapanor's effectiveness.

Participant Groups

Group I: Tenapanor Experimental Treatment 1 Intervention

30 mg Tenapanor twice a day

Group II: Placebo Placebo Group 1 Intervention

30 mg Placebo twice a day

Tenapanor is already approved in United States for the following indications:

🇺🇸 Approved in United States as Ibsrela for:

• Irritable Bowel Syndrome with Constipation (IBS-C)
• Chronic Kidney Disease

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UT Southwestern Medical Center Dallas, TX

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center Lead Sponsor

National Center for Advancing Translational Sciences (NCATS) Collaborator

References

1. France pubmed.ncbi.nlm.nih.gov

Setting, hardening and resorption of calcium phosphate hydraulic cements. [2013] Two examples of calcium phosphate hydraulic cements (CPHC) are presented. Type I cements consist in mixtures of beta-tricalcium phosphate (beta-TCP) and monocalcium phosphate monohydrate (MCPM), to which some plaster of Paris (CSH) is added as a setting retardant. Type II cements consist in mixtures of beta-TCP, dicalcium phosphate dihydrate (DCPD) and calcium carbonate (CC), to which some hydroxyapatite (HAP) is added as a setting accelerator. The setting time of these cements ranges from a few minutes up to a few hours, according to their composition and the amount of mixing water. Tensile strengths ranging from 1.2 up to 3.5 MPa have been recorded on cements which porosity ranged from 38 up to 55 vol%. In-vivo experiments on dogs have shown the perfect biocompatibility and resorbability of cement I.

2. United States pubmed.ncbi.nlm.nih.gov

Hydroxyapatite as an in-office agent for tooth hypersensitivity: a clinical and scanning electron microscopic study. [2022] Pain caused by hypersensitivity is very common and a variety of agents have been tried and tested to put an end to this ailment, but with limited or short-term success. The search for an agent that would predictably and permanently occlude the tubules and blend with them has prompted the use of durapatite/hydroxyapatite (HAP), which is the principal inorganic constituent of the tooth.

3. United States pubmed.ncbi.nlm.nih.gov

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 2. Physicochemical properties and drug release rate of the cement-containing indomethacin. [2019] A novel drug delivery device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro with indomethacin as a model drug. Equimolar mixtures of the calcium phosphate powders containing 2 and 5% of indomethacin were transformed into a hydroxyapatite after being mixed with a dilute phosphoric acid solution. X-ray diffraction and differential scanning calorimetry results suggested that indomethacin transformed into an amorphous form in the pores of the cement matrix as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for > 3 weeks. Release from 2 and 5% drug-loaded cements followed the Higuchi model equation. The drug release profiles of 5% drug-loaded cements with different thicknesses (0.5, 1.0, and 1.5 g) overlapped up to 90% drug release, indicating that the drug concentration gradient in the pore was independent of the thickness of the cement as expected from the model equation.

4. Netherlands pubmed.ncbi.nlm.nih.gov

Facile Synthesis and Characterization of Ibuprofen-mesoporous Hydroxyapatite Nanohybrid as a Sustained Drug Delivery System. [2020] The present study deals with the fabrication of ibuprofen-mesoporous hydroxyapatite (IBU-MHA) particles via the incorporation of ibuprofen (IBU)-as a nonsteroidal anti-inflammatory drug-into mesoporous hydroxyapatite nanoparticles (MHANPs) using an impregnation process, as a novel drug delivery device. MHANPs were synthesized by a self-assembly process using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant and 1-dodecanethiol as a pore expander under basic condition. The focus of the present study was to optimize the incorporation of IBU molecules into MHANPs under different loading conditions. The synthesized MHANPs and IBU-MHA particles were confirmed by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), brunauer-emmett-teller (BET), transmission electron microscopy (TEM), and thermal analysis (TGA). Drug loading (DL) efficiency of IBU-MHA particles was determined by ultraviolet-visible (UV-Vis) spectroscopy, and indicated that the optimized IBU-MHA particles with high DL (34.5%) can be obtained at an IBU/ MHANPs ratio of 35/50 (mg/mg), impregnation period of 24 h, and temperature of 40 °C using ethanol as solvent. In-vitro drug release test was carried out to prove the efficiency of IBU-MHA particles as a sustained drug delivery system. A more sustained and controlled drug release was observed for this particles, indicating that it may be have good potential as drug reservoirs for local drug release.

5. Netherlands pubmed.ncbi.nlm.nih.gov

Behaviour of an injectable calcium phosphate cement with added tetracycline. [2013] A calcium phosphate cement containing an antibiotic can be used for filling bone defects and to ensure local antibiotherapy. A calcium phosphate cement (already marketed under the name of Cementek can become injectable thanks to the addition of silicone. For dental applications, the behaviour of this injectable cement with added tetracycline was investigated. The tetracycline hydrochloride does not allow maturation of the cement: the tetracycline has to be treated with a calcium sulphate solution. The treated tetracycline (TTC) allowed maturation of the cement towards hydroxyapatite. But the setting time was longer and the mechanical properties decreased. Study in a continuous flow cell showed that the tetracycline is released in a continuous manner: thus, after 6 days, 60% of the antibiotic was released into the surrounding medium.