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

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.

Study Overview

• Status: Completed
• Conditions: Cystinuria
• Intervention / Treatment: Drug: Tiopronin

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cystinuria Patients	Drug: Tiopronin; Phase 1: No medication, Phase 2: 500mg PO daily x 7 days (total 500mg), Phase 3: 500mg PO BID x 7 days (total 1g), Phase 4: 1g PO BID x 7 days (total 2g)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cystine Capacity From Baseline	This measure reflects the ability of urine to take up more cystine	Baseline; Day 7

Collaborators and Investigators

• Sponsor: NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): September 10, 2019
• Study Completion (Actual): September 10, 2019

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 6, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): December 17, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Renal Tubular Transport, Inborn Errors; Renal Aminoacidurias; Cystinuria
• Other Study ID Numbers: 18-00642

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification. Researchers who provide a methodologically sound proposal.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing 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
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• 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