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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cystinuria

Intervention / Treatment
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* Drug: Tiopronin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cystinuria Patients<br> | Drug: Tiopronin<br>* 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)<br>|

What is the study measuring?
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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 |