Effect of Increasing Doses of Cystine Binding Thiol Drugs on Cystine Capacity in Patients With Cystinuria

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT02125721
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 66
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of escalating doses of cystine biding thiol drugs, including tiopronin and d-penicillamine, on the urinary cystine capacity, which is a measure of the amount of cystine in the urine, in patients with cystinuria. The overall goal will be to help guide therapy and ultimately minimize unnecessary side effects caused by larger doses.

Condition or Disease	Intervention/Treatment	Phase
Cystinuria	Drug: Tiopronin 1g per day; Drug: Tiopronin 2g per day; Drug: Tiopronin 3g per day	Phase 4

Detailed Description

Cystinuria is a rare genetic cause of kidney stones that leads to significant morbidity due to the recurrent nature of the disease. As a result, a significant part of treatment is focused on prevention of stone formation. Current methods of prevention include increasing fluid intake, dietary modifications, alkali therapy, and cystine binding thiol drugs (CBTDs), which help increase the solubility of cystine in the urine. At present, the dosing of CBTDs is empiric, and not titrated to a specific measured effect. Our primary objective will be to measure the effect of increasing doses of CBTDs on cystine capacity. The investigators predict that higher dosages of these medications will lead to a more positive urinary cystine capacity, or the ability of urine to take up more cystine (and therefore decreased risk of stone formation). However, the dose at which increasing dosages of the medications cease to provide additional benefit is unknown. The investigators will directly measure the cystine capacity in the urine in response to increasing doses of medications to determine if there is a dose at which the maximum benefit of the drug exists.

This is a cross-over trial of escalating doses. There will be four parts to the study. In the first part, subjects will stop taking CBTDs for 7 days, and perform a 24-hour urine collection on day 7. In part 2, they will take their usual CBTD (either tiopronin or d-penicillamine) 1 gram per day for 7 days. They will perform another 24-hour urine collection on day 7 of this study period. In part 3, they will take their usual CBTD at 2 grams per day for 7 days and in part 4 they will take their CBTD at 3 grams per day for 7 days. Again, they will perform 24-hour urine collections on day 7 of each period. The order in which the parts of the study are performed will be randomized for each subject. The mean cystine capacities in each part of the study will be compared to determine the effect of drug dosage on urinary cystine capacity.

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 Cystine Binding Thiol Drugs on Cystine Capacity in Patients With Cystinuria
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: CBTD Patients Part 1: patients will stop taking CBTDs for seven days and perform a 24-hour urine collection on day 7 Part 2: patients will take their usual CBTD, either tiopronin or d-penicillamine, 1g per day for 7 days, taken as 500 mg twice a day Part 3: patients will take a total of 2g of tiopronin or D-penicillamine daily for 7 days Part 4: patients will take a total of 3g/d of tiopronin or D-penicillamine, also for a 7 day period

Drug: Tiopronin 1g per day; 500mg PO BID x 7 days; Other Names: Thiola or tiopronin; d-penicillamine ; Drug: Tiopronin 2g per day; 1g PO BID x 7 days; Other Names: Thiola or tiopronin; d-penicillamine ; Drug: Tiopronin 3g per day; 1.5g PO BID x 7 days; Other Names: Thiola or tiopronin; d-penicillamine

Outcome Measures

Primary Outcome Measures

1. Cystine Capacity [4 weeks on assigned therapy]

   We will test for a negative correlation between progressive increases in doses of thiol drugs and cystine capacity

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Be a patient with a confirmed diagnosis of cystinuria.

• Be already taking a CBTD (either D-penicillamine (Cuprimine®) or tiopronin (Thiola®) as part of your medication regimen.

• Be between 18 and 80 years of age

• Be enrolled in the Cystinuria Registry.

Exclusion Criteria:

• You are not a patient with cystinuria

• You are not already taking a cystine binding thiol drug

• You have renal colic (if you are passing a stone)

• You are scheduled to undergo a urologic procedure

• You are unwilling or unable to provide informed consent in order to be able to participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU Langone Medical Center	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: David S Goldfarb, MD, NYU Langone Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 17, 2016

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT02125721
• Other Study ID Numbers: 16-00108; 1U54DK083908
• First Posted: Apr 29, 2014
• Last Update Posted: Aug 23, 2021
• Last Verified: Jul 1, 2021

• 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
• Keywords provided by NYU Langone Health: cystinuria; D-penicillamine (Cuprimine®); tiopronin (Thiola®)
• Additional relevant MeSH terms: Cystinuria; Penicillamine

Study Results

Participant Flow

Pre-assignment Detail	Participant flow data was not provided "per sequence". Multiple efforts were made to obtain information, but have not been successful.

Arm/Group Title	CBTD Patients
Arm/Group Description	Part 1: patients will stop taking CBTDs for seven days and perform a 24-hour urine collection on day 7 Part 2: patients will take their usual CBTD, either tiopronin or d-penicillamine, 1g per day for 7 days, taken as 500 mg twice a day Part 3: patients will take a total of 2g of tiopronin or D-penicillamine daily for 7 days Part 4: patients will take a total of 3g/d of tiopronin or D-penicillamine, also for a 7 day period
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	CBTD Patients
Arm/Group Description	Part 1: patients will stop taking CBTDs for seven days and perform a 24-hour urine collection on day 7 Part 2: patients will take their usual CBTD, either tiopronin or d-penicillamine, 1g per day for 7 days, taken as 500 mg twice a day Part 3: patients will take a total of 2g of tiopronin or D-penicillamine daily for 7 days Part 4: patients will take a total of 3g/d of tiopronin or D-penicillamine, also for a 7 day period
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	7 70%
Male	3 30%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	7 70%

Outcome Measures

1. Primary Outcome

Title	Cystine Capacity
Description	We will test for a negative correlation between progressive increases in doses of thiol drugs and cystine capacity
Time Frame	4 weeks on assigned therapy

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Increasing Doses of CBTD
Arm/Group Description	Intervention: CBTD 0-3 gm CBTD 0-3 gm: Oral CBTD 0-3 gm dose/day for 7 days, dose escalation
Measure Participants	7
Mean (Standard Deviation) [mg/L]	43.1 (131.2)

Adverse Events

Time Frame	10 Days
Adverse Event Reporting Description	Multiple efforts to contact the PI/study team for the relevant data have failed. Therefore, per intervention data are not available to be reported for this assessment.
Arm/Group Title	CBTD Patients
Arm/Group Description	Part 1: patients will stop taking CBTDs for seven days and perform a 24-hour urine collection on day 7 Part 2: patients will take their usual CBTD, either tiopronin or d-penicillamine, 1g per day for 7 days, taken as 500 mg twice a day Part 3: patients will take a total of 2g of tiopronin or D-penicillamine daily for 7 days Part 4: patients will take a total of 3g/d of tiopronin or D-penicillamine, also for a 7 day period
All Cause Mortality
	CBTD Patients
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	CBTD Patients
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	CBTD 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.