Wilson DiseaseNCT07301216
Off Treatment Urinary Copper Excretion in Wilson Disease, Pilot Study
An observational study of Wilson Disease, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Wilson Disease
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2026to 30 Sep 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hatice Maras, MD contact
United States1 site, 1 recruiting
- Recruiting
Yale School of Medicine
New Haven, Connecticut, 06520
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Wilson Disease
- Keywords
- Urine copper excretion, Non-ceruloplasmin bound copper
- Medical subject headings
- Hepatolenticular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: days 1, 2, 3 and 4 post stopping WD meds
Secondary outcomes (2)
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.
Measured: days 1, 2, 3 and 4 post stopping WD meds
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.
Measured: days 1, 2, 3 and 4 post stopping WD meds
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2025
- Study start8 Jan 2026
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Wilson DiseaseStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael L Schilsky, MD FAASLD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07301216
- Sponsor's protocol ID
- 2000040776
- Other IDs
- 1R01DK137861-01A1
- Status last verified
- Mar 2026
- First submitted
- 22 Dec 2025
- Last updated
- 5 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31948584Harrington 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;63(2):320-328. doi: 10.1515/cclm-2024-0213. Print 2025 Jan 29.
PubMed 39072400
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monitoring of Therapy in Wilson Disease With Off-Treatment Urinary Copper Excretion (OT-UCE): Comparison With Serum Non-Ceruloplasmin Copper (NCC) Assays
- ClinicalTrials.gov ID
- NCT07301216
- Acronym / sponsor ID
- 2000040776
- Conditions
- Wilson Disease
- Keywords
- Urine copper excretion, Non-ceruloplasmin bound copper
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 8 Jan 2026 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 24 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Mean concentration of OT-UCE for each standard of care WD treatment
Time frame: days 1, 2, 3 and 4 post stopping WD meds
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.
Mean NCC concentration for each WD treatment
Time frame: days 1, 2, 3 and 4 post stopping WD meds
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.
2 secondary outcomes
Mean OT-UCE Ranges for each WD med
Time frame: days 1, 2, 3 and 4 post stopping WD meds
Assess the best timepoints for performance of OT-UCE for each drug
Time frame: days 1, 2, 3 and 4 post stopping WD meds
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Background: PubMed 31948584Solovyev 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.
- Background: PubMed 39072400Harrington 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;63(2):320-328. doi: 10.1515/cclm-2024-0213. Print 2025 Jan 29.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hatice Maras, MD contact
Michael L Schilsky, MD FAASLD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Wilson Disease, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sefa Keserci, MD (203 737 2702, sefa.keserci@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean concentration of OT-UCE for each standard of care WD treatment (time frame: days 1, 2, 3 and 4 post stopping WD meds). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07301216, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.