TCUPS- Tolvaptan Use in Cystinuria and Urolithiasis: A Pilot Study

Study Overview
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Brief Summary
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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.

Official Title
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Use of Tolvaptan, a Vasopressin Antagonist, to Increase Urine Dilution and Reduce Cystine Urolithiasis Among Patients With Homozygous Cystinuria: a Pilot Investigation

Conditions
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Cystinuria

Intervention / Treatment
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* Drug: Tolvaptan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 29 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tolvaptan<br> | Drug: Tolvaptan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 23 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 11 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystinuria, Kidney Stones