Cystinuria
Conditions
Brief summary
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.
Interventions
DRUGTiopronin
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)
Sponsors
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cystine Capacity From Baseline | Baseline; Day 7 | This measure reflects the ability of urine to take up more cystine |
Countries
United States
Participant flow
Pre-assignment details
Multiple efforts to contact the PI/study team for the relevant data have failed. Therefore, per sequence data are not available to be reported for this assessment.
Participants by arm
| Arm | Count |
|---|---|
| Cystinuria Patients 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) | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Cystinuria Patients |
|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 15.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Cystine Capacity From Baseline
This measure reflects the ability of urine to take up more cystine
Time frame: Baseline; Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cystinuria Patients | Change in Cystine Capacity From Baseline | Phase 1 | -63.6 mg/L | Standard Deviation 24.8 |
| Cystinuria Patients | Change in Cystine Capacity From Baseline | Phase 2 | 76 mg/L | Standard Deviation 18.1 |
| Cystinuria Patients | Change in Cystine Capacity From Baseline | Phase 3 | 53.4 mg/L | Standard Deviation 17.7 |
| Cystinuria Patients | Change in Cystine Capacity From Baseline | Phase 4 | 103.1 mg/L | Standard Deviation 27.4 |