Tenapanor for Kidney Stones

Overseen By Jonathan M Whittamore, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

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 This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

10 Participants Needed

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}

Research Team

Jonathan M Whittamore, Ph.D.

Principal Investigator

University of Texas Southwestern Medical Center

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)

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

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

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Findings from Research

Type I calcium phosphate hydraulic cements (CPHC) show excellent biocompatibility and resorbability in in-vivo experiments on dogs, indicating their potential for safe use in medical applications.

The setting time and tensile strength of these cements can be adjusted based on their composition, with strengths ranging from 1.2 to 3.5 MPa and porosity between 38% and 55%, allowing for tailored applications in bone repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setting, hardening and resorption of calcium phosphate hydraulic cements. Lemaitre, J., Munting, E., Mirtchi, AA.[2013]

Hydroxyapatite (HAP) treatment significantly reduced hypersensitivity symptoms in patients, showing effectiveness at 1 day and up to 4 weeks after treatment, compared to control groups.

Scanning electron microscopy revealed that HAP completely occluded dentinal tubules, indicating its potential as a permanent desensitizer, although effects diminished by 8 weeks, suggesting the need for further long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxyapatite as an in-office agent for tooth hypersensitivity: a clinical and scanning electron microscopic study. Shetty, S., Kohad, R., Yeltiwar, R.[2022]

A new drug delivery device using bioactive cement made from tetracalcium phosphate and dicalcium phosphate effectively releases indomethacin over more than 3 weeks, demonstrating its potential for sustained drug delivery.

Indomethacin transforms into an amorphous form within the cement matrix, and the drug release follows the Higuchi model, indicating a consistent release profile that is not affected by the thickness of the cement.

NCBI (Pubmed)

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. Otsuka, M., Matsuda, Y., Suwa, Y., et al.[2019]

The study successfully created ibuprofen-loaded mesoporous hydroxyapatite (IBU-MHA) particles, achieving a high drug loading efficiency of 34.5% under optimized conditions, which included a specific ibuprofen to MHANPs ratio and a 24-hour impregnation period.

In vitro tests showed that IBU-MHA particles provide a sustained and controlled release of ibuprofen, suggesting they could be effective as drug delivery systems for localized treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facile Synthesis and Characterization of Ibuprofen-mesoporous Hydroxyapatite Nanohybrid as a Sustained Drug Delivery System. Namazi, Z., Jafarzadeh Kashi, TS., Erfan, M., et al.[2020]

The study demonstrates that an injectable calcium phosphate cement containing tetracycline can effectively fill bone defects while providing local antibiotic treatment, although the tetracycline must be treated with calcium sulfate to allow proper cement maturation.

While the treated tetracycline enables the cement to mature into hydroxyapatite, it results in a longer setting time and reduced mechanical properties, but still allows for a sustained release of 60% of the antibiotic over 6 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behaviour of an injectable calcium phosphate cement with added tetracycline. Ratier, A., Freche, M., Lacout, JL., et al.[2013]

References

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

Setting, hardening and resorption of calcium phosphate hydraulic cements. [2013]

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]

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]

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

Facile Synthesis and Characterization of Ibuprofen-mesoporous Hydroxyapatite Nanohybrid as a Sustained Drug Delivery System. [2020]

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

Behaviour of an injectable calcium phosphate cement with added tetracycline. [2013]