Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria

• ClinicalTrials.gov Identifier: NCT03663855
• Recruitment Status: Completed
• First Posted: September 10, 2018
• Last Update Posted: January 13, 2020
• Sponsor: NYU Langone Health
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

The purpose of this study is to determine the minimum effective dose of the cysteine binding thiol drug (CBTD) Tiopronin on urine cystine capacity, which is a measure of cystine solubility in the urine, in patients with cystinuria to evaluate the effect of escalating doses of cystine binding thiol drugs on the cystine capacity of the urine. The overall goal will be to help guide therapy and ultimately minimize unnecessary side effects caused by larger dosages.

Cystinuria is a rare genetic disease that can lead to significant morbidity in affected patients due to the recurrent nature of the disease. This study will follow the levels of urine cystine capacity in order to help guide treatment and to use lower than usually prescribed Tiopronin doses to decrease the potential side effects while maintaining therapeutic benefit. This will increase adherence with the medications by decreasing the burden of the large number of pills that need to be taken daily.

Condition or disease	Intervention/treatment	Phase
Cystinuria	Drug: 7 Days Tiopronin; Drug: 500 mg Tiopronin; Drug: 1 grams per day of Tiopronin; Drug: 2 grams per day of Tiopronin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria
• Actual Study Start Date: November 1, 2018
• Actual Primary Completion Date: September 10, 2019
• Actual Study Completion Date: September 10, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Cystinuria Patients

Drug: 7 Days Tiopronin; On day 7 of this period,patients will be asked to perform a 24-hour urine collection to measure the urinary cystine levels.; Drug: 500 mg Tiopronin; 5 tablets a day (200mg tab AM and 300mg tab PM). On day 7 of this period, you will perform a 24-hour urine collection.; Drug: 1 grams per day of Tiopronin; 5 tabs twice a day (100mg per tab). Patients will have another 24-hour urine collection on day 7 of this period.; Drug: 2 grams per day of Tiopronin; 10 tabs twice a day (100mg per tab). On day 7 of this period, patients will perform the final 24-hour urine collection.

Outcome Measures

Primary Outcome Measures :

1. Measure of Cystine Capacity [ Time Frame: 12 Months ]
   This measure reflects the ability of urine to take up more cystine

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with a confirmed laboratory diagnosis of cystinuria who meet the following criteria: (1) stone analysis demonstrating cystine as a component, or (2) increased urinary cystine excretion (>250mg/24hrs in adults).
• A medical regimen that includes Tiopronin.
• Willing to use a medically accepted form of birth control, if female and of child bearing- potential
• Ability to reliably urinate in a collection vessel and measure urine volume.
• Ability to give informed consent.
• Documentation of a stable complete blood count (CBC) and urinalysis (UA) in the six month period prior to the date of enrollment.
• Enrollment in Rare Kidney Stone Consortium (RKSC) Protocol 6401 (Cystinuria Registry)

Exclusion Criteria:

• Women who are pregnant, breastfeeding, or trying to become pregnant
• Patients with renal colic
• Patients who are scheduled to undergo a surgical procedure
• Inability to give informed consent

Contacts and Locations

Locations

United States, New York

New York University School of Medicine

New York, New York, United States, 10016

Sponsors and Collaborators

NYU Langone Health

Investigators

• Principal Investigator: David Goldfarb, MD; NYU Langone Health

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT03663855
• Other Study ID Numbers: 18-00642
• First Posted: September 10, 2018
• Last Update Posted: January 13, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All of the individual participant data collected during the trial, after deidentification. Researchers who provide a methodologically sound proposal.
• Supporting Materials: Clinical Study Report (CSR); Analytic Code
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting requests and accessing data may be found at (Link to be provided

• 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.: No

Additional relevant MeSH terms:

Cystinuria; Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases