The purpose of the study is to determine the effect of increasing doses of cystine binding thiol drugs (CBTDs) on the amount of cystine in the urine in
patients with cystinuria. There are 2 CBTDs: D-penicillamine (Cuprimine®) and tiopronin (Thiola®).
Cystinuria is a rare, inherited disease that results in the recurrent formation of kidney stones. Patients with cystinuria have an abnormality in the way
the kidneys handle the amino acid cystine (a molecule that joins with other amino acids to form a protein). As a result, the cystine accumulates in the
urine and forms crystals, which then join together to form stones.
The treatment of cystinuria is focused on preventing the formation of kidney stones. Methods to do so involve increasing the ability of the urine to
dissolve cystine. This is done by increasing fluid intake, making dietary changes, taking medications called alkalinizing agents (potassium citrate, sodium
bicarbonate) to lower the acidity of the urine to make it less favorable to form stones, and by taking CBTDs that bind cystine and lower its concentration
in the urine. These cystine binding thiol drugs include D-penicillamine (Cuprimine®) and tiopronin (Thiola®).
This study aims to find the dose of CBTD that will most effectively lower the amount of cystine in the urine. Although CBTDs have been in use for many
years, the dosing is really based on guess-work and no studies to date have compared the effect of different doses on the amount of cystine in the urine.
The hope is to find the minimum dose that is effective so that side effects from unnecessary, larger doses can be avoided.
The cystine in the urine will be measured directly with a lab test called the cystine capacity (CysCap), which was developed by Litholink Corporation, a
commercial laboratory, in Chicago, IL. The levels will be measured in response to increasing doses of the medications to see if there is a dose at which a
maximum benefit exists. Overall, the hope is to tailor the medication doses to the effect on the urine in order to reduce side effects and improve the
quality of life for patients with cystinuria.
The research questions are:
- What is the effect of escalating doses of CBTDs on the cystine capacity of the urine in patients with cystinuria?
- Is there a maximum dose at which further increases in dose provide no further benefit?
About this Study
The plan is to have 10 to 15 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 be asked to participate in the following:
- Sign a consent form indicating your willingness to participate in this study
- Have a documented complete blood count (CBC) and urinalysis (UA) performed in the 6 month period prior to study
- The order of the following 4 steps will be different in each participant:
- Stop their CBTD (either D-penicillamine (Cuprimine®) or tiopronin (Thiola®)) for 7 days and perform a 24-hour urine collection on day 7
- Take their usual CBTD at a dose of 1 gram per day for 7 days, and perform a 24-hour urine collection on day 7
- Take their usual CBTD at a dose of 2 grams per day for 7 days, and perform a 24-hour urine collection on day 7
- Take their usual CBTD at a dose of 3 gram per day for 7 days, and perform a 24-hour urine collection on day 7
- Keep a food and fluid intake diary in the first part of the study on the day prior to and the day of the urine collection, and then repeat it in the subsequent study periods
- Repeat a blood test for complete blood count and a urine test for a urinalysis within one month of completion of the study
To be eligible to participate, you must meet all of the following criteria:
- Have a confirmed diagnosis of cystinuria.
- Already take 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.
You are not eligible to participate if ANY one of the following apply:
- You do not have a confirmed diagnosis of cystinuria
- You are not already taking a CBTD (either D-penicillamine (Cuprimine®) or tiopronin (Thiola®))
- 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.
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.
New York University, New York City
Contact: Frank Modersitzki
Phone: 212-686-7500 Ext: 6379