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

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT03663855
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 10.3
• Patients Per Site Per Month: 1

Study Details

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: Tiopronin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 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: Nov 1, 2018
• Actual Primary Completion Date: Sep 10, 2019
• Actual Study Completion Date: Sep 10, 2019

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Change in Cystine Capacity From Baseline [Baseline; Day 7]

   This measure reflects the ability of urine to take up more cystine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 15, 2019

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT03663855
• Other Study ID Numbers: 18-00642
• First Posted: Sep 10, 2018
• Last Update Posted: Dec 17, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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

Study Results

Participant Flow

Pre-assignment Detail	Multiple efforts to contact the PI/study team for the relevant data have failed. Therefore, per sequence data are not available to be reported for this assessment.

Arm/Group Title	Cystinuria Patients
Arm/Group Description	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)
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Cystinuria Patients
Arm/Group Description	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)
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.3 (15.42)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	9 90%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cystinuria Patients
Arm/Group Description	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)
Measure Participants	10
Phase 1	-63.6 (24.8)
Phase 2	76 (18.1)
Phase 3	53.4 (17.7)
Phase 4	103.1 (27.4)

Adverse Events

Time Frame	30 days
Adverse Event Reporting Description	Multiple efforts to contact the PI/study team for the relevant data have failed. Therefore, per dose level data are not available to be reported for this assessment.
Arm/Group Title	Cystinuria Patients
Arm/Group Description	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)
All Cause Mortality
	Cystinuria Patients
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Cystinuria Patients
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Cystinuria Patients
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.