6421: Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients with Cystinuria

Status: Recruiting

Background

The purpose of this study is to determine the effect of increasing dosages of tiopronin (Thiola®) on the solubility of cystine in the urine of individuals with cystinuria. Cystinuria is a rare inherited disease that results in the frequent formation of kidney stones. Patients with cystinuria have an abnormality in the way the kidneys handle cystine, an amino acid. This abnormality results in an excessive amount of cystine excreted into the urine. Cystine does not dissolve well in urine and therefore, compacts together to form stones.

This study hopes to find the best dosage of tiopronin that should be given to cystinuria patients in order to allow the urine to take up more cystine and thus reduce the chance of kidney stones. There is no set guideline to the best prescribed dosage of tiopronin. It would be useful to dose the drug based on the urine chemistry.

This study will directly measure the cystine capacity (solubility of cystine in the urine) in response to increasing doses of tiopronin to determine if there is a dose at which the maximum benefit of the drug exists. This test will be useful to help guide therapy and ultimately minimize unnecessary side effects caused by large dosages. The cystine capacity will be measured by using a test called CysCap, which was developed by the Litholink Corporation. Overall, we hope that tailoring the drug doses to the effect on the urine cystine will improve the treatment and quality of life for patients with cystinuria.

You are being asked to participate in this study because you have cystinuria and are currently taking the Food and Drug Administration (FDA) approved medication tiopronin (Thiola®).

Funding for this research study is provided by the National Institutes of Health (NIH). The funding is used to support the activities of the Division of Nephrology to pay back the Division for the costs of the study personnel. Compensation is not based upon the number of people enrolled in the study. If your doctor is an investigator for this study, he is interested in both your healthcare and the conduct of this research. You do not have to take part in a research study conducted by your doctor.

The research questions are:

  1. What is the effect of escalating doses of tiopronin on the cystine capacity of the urine in patients with cystinuria?
  2. Is there a maximum dose at which further increases in dose provide no further benefit?

About this Study

The plan is to have 10 people take part in this single-center study.
The study duration is a total of 4 weeks. There are four parts to the study, each lasting 1 week.

Participants who agree to be in the study will do the following:

  1. You will sign and date this informed consent form after you have had all of your questions answered and decided you will like to participate.
  2. If you decide to participate, we will start with a screening interview. In the interview, you will be asked about your medical history, specifically your history of cystinuria, as well as your dietary habits. We will also review the medications you take and your most recent blood and urine tests. The interview should last approximately 20 minutes.
  3. There are four parts to the study. You will be randomly assigned an order to complete them in. By randomizing you, it ensures that you will be assigned to a group by chance (like flipping a coin). You will have an equal chance of being in any group of the study. The four parts are as follows:
    1. In one part, you will be asked to stop taking your tiopronin for 7 days. You should continue taking all of your other medications as prescribed during this time. On day 7 of this period, we will ask you to perform a 24-hour urine collection to measure the urinary cystine levels.
    2. In a second part of the study, we will ask you to take tiopronin at a dose of 500mg per day. You will take 2 tablets in the morning and 3 tablets in the afternoon (200mg tab AM and 300mg tab PM). On day 7 of this period, you will perform a 24-hour urine collection.
    3. In a third part of the study, we will ask you to take 1 gram per day of tiopronin, divided in two doses: 500mg twice a day. You will take 10 tabs twice a day (100mg per tab). You will then perform another 24-hour urine collection on day 7 of this period.
    4. In a fourth part of the study, we will ask you to take 2 grams per day of tiopronin, divided in two doses. You will take 10 tabs twice a day (100mg per tab). On day 7 of this period, you will perform the final 24-hour urine collection.
  4. You will be on your own diet during the study. However, we will ask you to keep a food and fluid intake diary on the day before and the day on each of the four urine collections. In addition, please try to repeat the same diet and fluid intake on the day before and the day of each urine collection.
  5. We will provide you with all of the materials to perform the four separate urine collections and to have each sent to Litholink, the laboratory performing the analysis of your urine. This will be provided to you at no cost.
  6. We will provide you with a prescription for tiopronin (Thiola®) for enough pills to cover the amount needed to participate in the study. We will provide compensation for any additional costs for the medications used in the study that are not covered by your primary insurance.
  7. At the end of the four-week study period, after the fourth urine collection, we will ask you to restart your home dose tiopronin, as prescribed by your primary nephrologist/physician.
  8. You will be asked to complete a blood test (complete blood count) and urine test (urinalysis) within 6 month of completing the study to monitor for any possible adverse effects from the changes in medications.

You will be contacted weekly to answer questions about your general health and wellbeing during the four-week study period.

Targeted Enrollment

To be eligible to participate, you must meet ALL of the following criteria:

  • Age between 18 and 80 years.
  • 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)

You are not eligible to participate if ANY one of the following apply:

  • 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

How to participate

In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.

United States

New York

Rare Kidney Stone Consortium
Cystinuria Program

New York University
423 East 23 Street, 111G
VA New York Harbor Healthcare System
Veterans Administration
New York, NY 10010

Contact: Frank Modersitzki, MPH
Phone: 212-686-7500, ext. 6379
E-mail: Frank.Modersitzki@nyumc.org