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

• ClinicalTrials.gov Identifier: NCT02125721
• Recruitment Status: Completed
• First Posted: April 29, 2014
• Last Update Posted: April 5, 2018
• Sponsor: NYU Langone Health
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): NYU Langone Health

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: CBTD 0-3 gm	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 (Clinical Trial)
• 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: June 2012
• Actual Primary Completion Date: December 2017
• Actual Study Completion Date: December 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Increasing doses of CBTD; Intervention: CBTD 0-3 gm	Drug: CBTD 0-3 gm; Oral CBTD 0-3 gm dose/day for 7 days, dose escalation; Other Name: Thiola or tiopronin; d-penicillamine

Outcome Measures

Primary Outcome Measures :

1. Cystine capacity [ Time Frame: 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

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

Criteria

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

United States, New York

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

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT02125721
• Other Study ID Numbers: 16-00108; 1U54DK083908 ( U.S. NIH Grant/Contract )
• First Posted: April 29, 2014
• Last Update Posted: April 5, 2018
• Last Verified: April 2018

• 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; Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Penicillamine; Antidotes; Protective Agents; Physiological Effects of Drugs; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents