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

• Sponsor: Caleb Nelson (Other)
• Overall Status: Completed
• CT.gov ID: NCT02538016
• Collaborator: Otsuka America Pharmaceutical (Industry)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 26
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystinuria	Drug: Tolvaptan	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Use of Tolvaptan, a Vasopressin Antagonist, to Increase Urine Dilution and Reduce Cystine Urolithiasis Among Patients With Homozygous Cystinuria: a Pilot Investigation
• Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Tolvaptan	Drug: Tolvaptan

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 29 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Children's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Caleb Nelson
• Otsuka America Pharmaceutical

Investigators

• Principal Investigator: Caleb Nelson, MD, MPH, Boston Children's Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 23, 2019

More Information

Publications

None provided.

• Responsible Party: Caleb Nelson, MD, MPH, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT02538016
• Other Study ID Numbers: 16726
• First Posted: Sep 2, 2015
• Last Update Posted: Jul 10, 2020
• Last Verified: May 1, 2020

• Keywords provided by Caleb Nelson, MD, MPH, Boston Children's Hospital: Cystinuria; Kidney Stones
• Additional relevant MeSH terms: Urolithiasis; Urinary Calculi; Cystinuria; Tolvaptan

Study Results

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 Detail	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.

Arm/Group Title	Tolvaptan
Arm/Group Description	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.
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Tolvaptan
Arm/Group Description	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.
Overall Participants	4
Age (Count of Participants)
<=18 years	2 50%
Between 18 and 65 years	2 50%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Urinary Cystine Supersaturation (mg/L) at High Dose (Day7-8)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolvaptan
Arm/Group Description	Tolvaptan.
Measure Participants	4
Mean (Full Range) [mg/L]	70

2. Secondary Outcome

Title	Urine Osmolality at High Dose (Day 8)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolvaptan
Arm/Group Description	Tolvaptan.
Measure Participants	4
Sodium	141
Potassium	4.05
Chloride	102

Adverse Events

Time Frame	2 weeks
Arm/Group Title	Tolvaptan
Arm/Group Description	Tolvaptan.
All Cause Mortality
	Tolvaptan
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Tolvaptan
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Tolvaptan
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Investigations
Severe Thirst	4/4 (100%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.