Cystinuria
Conditions
Keywords
Cystinuria, Kidney Stones
Brief summary
The goal of this research project is to establish that in short-term use, tolvaptan is a safe and potentially effective new therapy for cystinuria, by conducting a short-term pilot study of the safety and tolerability of this drug, and assess impact on urinary stone risk parameters, among adolescent and young adult patients with clinical cystinuria.
Interventions
DRUGTolvaptan
Sponsors
Otsuka America Pharmaceutical
Caleb Nelson
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 29 Years
Healthy volunteers
No
Inclusion criteria
* Males and females age 12 - 29 years * Weight ≥ 25kg (55 lbs) * Confirmed cystinuria diagnosis * Specific blood test levels (done within the past 6 months)
Exclusion criteria
* Concurrent non-renal disease that might increase risk of complications due to aquaresis * Liver or biliary disease (chronic or acute) * Malabsorption syndrome or other gastrointestinal condition that may interfere with response to therapy * Non-cutaneous malignancy within last 5 years * History of adverse reaction or allergy to Tolvaptan or other arginine vasopressin V2-receptor antagonists
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Cystine Supersaturation (mg/L) at High Dose (Day7-8) | 23 days | The primary outcome was urinary cystine supersaturation as measured by cystine capacity. This proprietary test (Litholink Corp., Chicago IL) is reported as a value in mg/L above or below zero, with positive values indicating urine undersaturated with cystine, while negative values indicate that the urine is supersaturated with cystine. Four 24-hour urine samples were obtained during the study: one at baseline 3-6 days prior to the measurement, one on day 3-4 of the dosing period, one on day 7-8 of the dosing period, and one 3-6 days after the washout period. Each 24 hour urine sample was sent individually for analysis by Litholink Corp, which performs the cystine assays. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine Osmolality at High Dose (Day 8) | 11 days | Secondary outcomes included serum sodium and other electrolyte levels. Serum electrolytes for each subject before, during, and after tolvaptan treatment (Sodium/Potassium/Chloride in mmol/L). |
Countries
United States
Participant flow
Recruitment details
Recruitment and Enrollment period was between August 2016 to December 2018. Subjects were recruited from our existing database of cystinuria patients, from new patients presenting during the research period, and via advertising through the International Cystinuria Foundation, Rare Kidney Stone Consortium, and social media.
Pre-assignment details
Of 6 eligible and interested participants, 5 met inclusion criteria and were consented, and of these, 1 withdrew prior to travel to our hospital for drug administration.
Participants by arm
| Arm | Count |
|---|---|
| Tolvaptan This was a single arm, unblinded study. All participants received half of the recommended dose (weight-dependent) on Days 1 through 4 and then the full recommended dose (weight-dependent) on Days 5 through 8
Example of Dosing Schedule by Weight:
Participant Weight is between: 12.5 kg -37.49 kg Then their Dose on Days 1-4 = 7.5mg (.6mg/kg -.2mg/kg) Dose on Days 5-8 is doubled = 15mg (1.2mg/kg - .4mg/kg) Maximum dose administered was 60 mg. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Tolvaptan | — |
|---|---|---|
| Age, Categorical <=18 years | 2 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 2 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 2 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Urinary Cystine Supersaturation (mg/L) at High Dose (Day7-8)
The primary outcome was urinary cystine supersaturation as measured by cystine capacity. This proprietary test (Litholink Corp., Chicago IL) is reported as a value in mg/L above or below zero, with positive values indicating urine undersaturated with cystine, while negative values indicate that the urine is supersaturated with cystine. Four 24-hour urine samples were obtained during the study: one at baseline 3-6 days prior to the measurement, one on day 3-4 of the dosing period, one on day 7-8 of the dosing period, and one 3-6 days after the washout period. Each 24 hour urine sample was sent individually for analysis by Litholink Corp, which performs the cystine assays.
Time frame: 23 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tolvaptan | Urinary Cystine Supersaturation (mg/L) at High Dose (Day7-8) | 70 mg/L |
Secondary
Urine Osmolality at High Dose (Day 8)
Secondary outcomes included serum sodium and other electrolyte levels. Serum electrolytes for each subject before, during, and after tolvaptan treatment (Sodium/Potassium/Chloride in mmol/L).
Time frame: 11 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tolvaptan | Urine Osmolality at High Dose (Day 8) | Sodium | 141 mmol/L |
| Tolvaptan | Urine Osmolality at High Dose (Day 8) | Potassium | 4.05 mmol/L |
| Tolvaptan | Urine Osmolality at High Dose (Day 8) | Chloride | 102 mmol/L |