Effect of Increasing Doses of Cystine Binding Thiol Drugs on Cystine Capacity in Patients With Cystinuria
Condition: Cystinuria
MeSH terms: Cystinuria
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Tiopronin 1g per day; Tiopronin 2g per day; Tiopronin 3g per day
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 500mg PO BID x 7 days; 1g PO BID x 7 days; 1.5g PO BID x 7 days
Other intervention name(s): Thiola or tiopronin; d-penicillamine; Thiola or tiopronin; d-penicillamine; Thiola or tiopronin; d-penicillamine
Intervention MeSH terms: Penicillamine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: cystinuria; D-penicillamine (Cuprimine®); tiopronin (Thiola®)