Off Treatment Urinary Copper Excretion in Wilson Disease, Pilot Study

Monitoring of Therapy in Wilson Disease With Off-Treatment Urinary Copper Excretion (OT-UCE): Comparison With Serum Non-Ceruloplasmin Copper (NCC) Assays

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.

Study procedures will include providing multiple urine samples over a 24-hour period, storing the urine samples, and returning them during the end-of-study visit. Blood samples will be collected to measure copper levels and liver function. An in-person end-of-study visit will be attended.

Participation in this study will involve a brief stoppage of current Wilson Disease treatment.

Participants will perform 24-hour urine collections and communicate with study personnel daily during the brief time medication is not taken.

At the end-of-study visit, the investigators will collect urine samples, obtain blood samples, perform a physical exam, and review safety evaluations (communication with study personnel) made during the study.

Inclusion Criteria:

• 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.
• Aminotransferase values (ASAT and ALAT) < 2 times the upper limit of normal (ULN).
• INR < 1.5 or stable INR for those with initial elevated INR for at least six months prior to study entry in the absence of anticoagulation therapy.
• Renal function defined as eGFR > 30 cc/min.
• No change of WD therapy during the previous 6 months of study enrollment.

Exclusion Criteria:

• 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

• Investigator believes the patient will be unable to do the required 24-hour urine studies and participate in the follow up visits as expected.

• Previous non-compliance for therapy and/or to low-copper diet that would compromise the evaluation of previous UCE and/ or results from the off-treatment period.

  • Childbearing aged patients recruited outside of the registry will be reviewed, and the patients will be asked to perform an initial urine pregnancy test prior to the recommended blood testing (approximately 60 to 90 days prior to intervention). They will be permitted to continue with the screening process if the result is negative. They will be asked to perform a second urine pregnancy test as close as possible prior to study intervention (discontinuation of treatment). If the result of the second pregnancy test is negative they will be permitted to continue with the protocol, but if the result is positive they will be excluded from further participation at that time.

Childbearing aged patients recruited from the registry who meet inclusion criteria and may move directly to the study intervention will be required to perform a urine pregnancy test as close as possible to the time prior to the initiation of the study protocol (discontinuation of treatment).