Off Treatment Urinary Copper Excretion in Wilson Disease, Pilot Study

NCT07301216 | Recruiting

• 2 other identifiers: 20000407761R01DK137861-01A1
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Wilson Disease

Keywords

Urine copper excretion; Non-ceruloplasmin bound copper

Outcome Measures

Primary Outcomes (2)

• 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.

  days 1, 2, 3 and 4 post stopping WD meds

• 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.

  days 1, 2, 3 and 4 post stopping WD meds

Secondary Outcomes (2)

• Mean OT-UCE Ranges for each WD med

  days 1, 2, 3 and 4 post stopping WD meds

• Assess the best timepoints for performance of OT-UCE for each drug

  days 1, 2, 3 and 4 post stopping WD meds

Study Arms (3)

OT-UCE and NCC for Zinc treated WD patients

OT-UCE and NCC will be measured in WD patients on Zinc therapy

OT-UCE and NCC for Trientine treated WD patients

OT-UCE and NCC will be measured in WD patients on trientine therapy

OT-UCE and NCC for Penicillamine treated WD patients

OT-UCE and NCC will be measured in WD patients on Penicillamine therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Yale University: lead

Study Sites (1)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

RECRUITING

Related Publications (2)

• Solovyev N, Ala A, Schilsky M, Mills C, Willis K, Harrington CF. Biomedical copper speciation in relation to Wilson's disease using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry. Anal Chim Acta. 2020 Feb 15;1098:27-36. doi: 10.1016/j.aca.2019.11.033. Epub 2019 Nov 15.

  PMID: 31948584 BACKGROUND

• Harrington CF, Carpenter G, Coverdale JPC, Douglas L, Mills C, Willis K, Schilsky ML. Accurate non-ceruloplasmin bound copper: a new biomarker for the assessment and monitoring of Wilson disease patients using HPLC coupled to ICP-MS/MS. Clin Chem Lab Med. 2024 Jul 30:10.1515/cclm-2024-0213. doi: 10.1515/cclm-2024-0213. Online ahead of print.

  PMID: 39072400 BACKGROUND

MeSH Terms

Conditions

Hepatolenticular Degeneration

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Michael L Schilsky, MD FAASLD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sefa Keserci, MD

CONTACT

203 737 2702; sefa.keserci@yale.edu

Hatice Maras, MD

CONTACT

hatice.maras@yale.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: December 24, 2025
• Study Start: January 8, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)