Off Treatment Urinary Copper Excretion in Wilson Disease, Pilot Study
ConditionWilson Disease
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorYale University
About this trial
This is a prospective study that will determine the optimal timing for 24-hour urinary copper excretion (UCE) measurement after temporary discontinuation of standard therapies in Wilson Disease (WD) patients. The primary objective is to assess whether off-treatment UCE (OT-UCE) correlates with non-ceruloplasmin-bound copper (NCC) levels, aiming to validate OT-UCE as a surrogate marker for systemic copper bioavailability and disease stability. Stable WD patients will be enrolled, temporarily taken off treatment under close monitoring, and undergo UCE and NCC testing. If OT-UCE is validated, it could serve as a practical biomarker for monitoring WD treatment and stability in clinical practice and future trials.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with Wilson Disease as defined by Leipzig score ≥4.
Provision of signed and dated informed consent form.
Stated willingness to comply with all study procedures (serial 24 h urine collections and local collection of samples for NCC, liver function and estimated GFR) and availability for the duration of the study.
Treated WD for at least 12 months prior to study entry.
Disqualifiers
Current dual / mixed therapy for WD (i.e. zinc and d-penicillamine or trientine at the same time)
Current Pregnancy or lactation. *
Recent estrogen-based treatment (in the last month).
Cirrhosis with recent hepatic decompensation (within the last 6 months) - new onset of ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, or hepatic encephalopathy
Trial population
Patients with confirmed Wilson Disease (Leipzig score ≥4), and stable disease will be screened and recruited for this pilot. This will include patients 18 years old and above as the intervention for this study is a temporary discontinuation of therapy, and this group of patients will tolerate this intervention with minimal risk.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
30 Participants
are grouped into 3 trial groupsGroup A: OT-UCE and NCC for Zinc treated WD patients
Group B: OT-UCE and NCC for Trientine treated WD patients
Group C: OT-UCE and NCC for Penicillamine treated WD patients
Trial outcomes
Primary outcomes
1
Mean concentration of OT-UCE for each standard of care WD treatment
Urine samples will be collected daily for 4 days after stopping WD medications. The sequential evaluation of OT-UCE over a maximum of 4 days after treatment withdrawal will allow investigators to define the optimal ranges for UCE and select the best time-point for OT-UCE evaluations for WD patients on the 3 different therapies.
Time frame
days 1, 2, 3 and 4 post stopping WD meds2
Mean NCC concentration for each WD treatment
Measure NCC and assess the correlation between NCC and OT-UCE Urine samples will be collected daily for 4 days after stopping WD medications. The sequential evaluation of NCC over a maximum of 4 days after treatment withdrawal will allow investigators to assess the correlation between NCC and OT-UCE.
Time frame
days 1, 2, 3 and 4 post stopping WD medsSecondary outcomes
1
Mean OT-UCE Ranges for each WD med
Urine samples will be collected daily for 4 days after stopping WD medications. The sequential evaluation of OT-UCE over a maximum of 4 days after treatment withdrawal will allow investigators to define the optimal ranges for UCE for WD patients on the 3 different therapies.
Time frame
days 1, 2, 3 and 4 post stopping WD meds2
Assess the best timepoints for performance of OT-UCE for each drug
The day (or the minimal number of consecutive days) after treatment interruption at which 24-hour OT-UCE stabilizes (defined as a plateau with less than 10% variability between two consecutive measurements) for each drug (zinc, penicillamine, trientine). This will define the optimal timing of OT-UCE monitoring for each treatment.
Time frame
days 1, 2, 3 and 4 post stopping WD medsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Yale University
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Source ClinicalTrials.gov