Off Treatment Urinary Copper Excretion in Wilson Disease, Pilot Study

NCT ID: NCT07301216

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2026-02-28

Study Completion Date

2027-02-28

Brief Summary

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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.

Detailed Description

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Study procedures will include providing multiple urine samples over a 24-hour period, storing the urine samples and returning them during your end of study visit, providing blood samples to measure copper levels and liver function, and attending an in person end of study visit. Participation in this study will involve a brief stoppage of your current Wilson Disease treatment. You will perform 24-hour urine collections and communicate with study personnel daily during the brief time you are not taking your medication. At the end of study visit we will collect your urine samples, obtain blood samples, perform a physical exam, and review safety evaluations (communication with study personnel) made during the study.

Conditions

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Wilson Disease

Keywords

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Urine copper excretion Non-ceruloplasmin bound copper

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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OT-UCE and NCC for Zinc treated WD patients

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

No interventions assigned to this group

OT-UCE and NCC for Trientine treated WD patients

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

No interventions assigned to this group

OT-UCE and NCC for Penicillamine treated WD patients

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

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael L Schilsky, MD FAASLD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Yale School of Medicine

New Haven, Connecticut, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Sefa Keserci, MD

Role: CONTACT

Phone: 203 737 2702

Email: [email protected]

Hatice Maras, MD

Role: CONTACT

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 31948584 (View on PubMed)

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. doi: 10.1515/cclm-2024-0213. Online ahead of print.

Reference Type BACKGROUND
PMID: 39072400 (View on PubMed)

Other Identifiers

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1R01DK137861-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000040776

Identifier Type: -

Identifier Source: org_study_id