Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration

NCT ID: NCT05190744

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2025-12-31

Brief Summary

The purpose of this research is to study the effectiveness and safety of the medication PB in slowing the frequent urination related to tolvaptan as long-term treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD), or frequent urination related to inherited nephrogenic diabetes insipidus as an inherited condition or as an acquired condition from prior treatment with lithium.

Conditions

Autosomal Dominant Polycystic Kidney Disease; Nephrogenic Diabetes Insipidus; Acquired Nephrogenic Diabetes Insipidus; Congenital Nephrogenic Diabetes Insipidus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Polyuric subjects with Hereditary Nephrogenic Diabetes Insipidus

Polyuric subjects with hereditary nephrogenic diabetes insipidus with loss of function of arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2) will be treated with PB

Group Type: EXPERIMENTAL

PB

Intervention Type: DRUG

1000mg twice daily (BID). The dose of PB inducing the maximal increase in urine osmolality will be continued for up to four weeks providing that no side effects are observed including clinical and laboratory surveillance.

Polyuric subjects with Autosomal Dominant Polycystic Kidney Disease treated with Tolvaptan

Polyuric subjects with autosomal dominant polycystic kidney disease on chronic tolvaptan treatment will be treated with PB

Group Type: EXPERIMENTAL

PB

Intervention Type: DRUG

1000mg twice daily (BID). The dose of PB inducing the maximal increase in urine osmolality will be continued for up to four weeks providing that no side effects are observed including clinical and laboratory surveillance.

Polyuric subject secondary to lithium administration

Polyuric subject post lithium administration will receive PB

Group Type: EXPERIMENTAL

PB

Intervention Type: DRUG

1000mg twice daily (BID). The dose of PB inducing the maximal increase in urine osmolality will be continued for up to four weeks providing that no side effects are observed including clinical and laboratory surveillance.

Interventions

PB

1000mg twice daily (BID). The dose of PB inducing the maximal increase in urine osmolality will be continued for up to four weeks providing that no side effects are observed including clinical and laboratory surveillance.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female, ≥ 18 years of age (inclusive) at time of screening
• Diagnosis of one of the following:

1. ADPKD(as delineated in cohort 1)

2. Congenital NDI (as delineated in cohort 1)

3. Lithium-induced NDI (as delineated in cohort 1)

• Glomerular filtration rate (GFR) ≥ 25 ml/min/1.73 m2 at time of screening visit calculated as in cohort
• 24 hours urine volume in baseline 1 visit ≥ 5000 ml/ day
• If hypertensive, blood pressure controlled on antihypertensives (<130/80 mm Hg) at least 30 days before day 1. Antihypertensives may be adjusted at time of baseline 2 per PI discretion.
• Have read, understood, and provided written informed consent after the nature of the study has been fully explained and must be willing to comply with protocol requirements and study-related procedures.
• Negative urinary pregnancy test (if applicable) at baseline 2
• Capable of providing urine samples as dictated by the protocol

Exclusion Criteria

• Advanced diabetes (e.g., glycosylated hemoglobin [HgbA1c] >7.5%, and/or glycosuria by dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), other significant kidney disease, kidney cancer, transplanted kidney, single kidney, kidney surgery within the past 6 months (including cyst drainage or fenestration) or acute kidney injury within 6 months prior to screening.
• Clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia).
• Other significant chronic medical disease (heart failure, diabetes mellitus, liver disease, transient or persistent elevated transaminases)
• History of acute gout attack in the past 30 days
• History of clinically significant drug or alcohol abuse in the 2 years prior to screening visit.
• Uncontrolled hyperuricemia or active gout
• History of hepatotoxicity related to tolvaptan; or clinically significant liver disease or impairment; or alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin values >1.2 x Upper Limit of Normal (ULN) during screening.
• Medical history or findings that preclude safe participation in the trial or participants who are likely to be non-compliant with trial procedures in the opinion of the investigator or medical monitor.
• Requirement for ongoing diuretic use.
• Participants who are currently taking, or are expected to be taking, strong or moderate CYP3A4 or CYP2C8 inhibitors or inducers including regular use of grapefruit juice, Seville oranges, or St. John's wort. If applicable, there should be a 14-day washout of these treatments prior to Day 1.
• Prior use of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) (e.g., canagliflozin, dapagliflozin, empagliflozin, etc.) within the 2 months prior to screening visit or expected need for initiation of treatment with a SGLT2i inhibitor during the study. Current use of SGLT2i will be reviewed by PI and allow enrollment if patient has been on stable dose for at least 2 months.
• Prior use of a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor within the 2 months prior to screening visit or expected need for initiation of treatment with a HIF-PH inhibitor during the study;
• Participants who have taken any investigational drug or used an investigational device within 30 days, or 5 half-lives, whichever is longer, prior to screening visit 1a or plan to participate in an interventional trial during the study.
• Allergy to probenecid
• History of persistent hyponatremia
• Positive test results for hepatitis B surface antigen (HBsAg).
• Positive test results for hepatitis C (HCV) antibody (Anti-HCV), with the exception of participants for whom the reflex HCV RNA titer test is negative.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka America Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Fouad T. Chebib

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fouad Chebib, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Jacksonville, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Trinity Hooks

Role: CONTACT

Hooks.Trinity@mayo.edu

904-953-3057

Taylor Cunningham

Role: CONTACT

Cunningham.Taylor@mayo.edu

904-953-3292

Facility Contacts

Clinical Studies Unit

Role: primary

Hooks.Trinity@mayo.edu

904-953-3057

Taylor Cunningham

Role: backup

Cunningham.Taylor@mayo.edu

904-953-3292

Related Links

https://www.mayo.edu/research/clinical-trials/cls-20525492

Mayo Clinic Clinical Trials

Other Identifiers

21-005437

Identifier Type: -

Identifier Source: org_study_id