Wilson's DiseaseNCT07462026
Exchangeable and Relative Exchangeable Copper as an Alternative to 24-Hour Urinary Copper in Wilson's Disease Monitoring
An observational study of Wilson's Disease, run by Hacettepe University at 1 site in Turkey (Türkiye).
Trial summary
Serum exchangeable copper (EC) and relative exchangeable copper (REC) are blood tests developed to improve the assessment of copper levels in patients with Wilson's disease. EC measures the fraction of copper in the blood that is not bound to ceruloplasmin and reflects copper accumulation in the body. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Wilson's Disease
- How many people
- 81 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 31 Jan 2021to 5 Sep 2021
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: The study population consisted of adult patients with Wilson's disease who were followed at the gastroenterology and neurology outpatient clinics of a tertiary university hospital. A control population was selected from adult patients presenting with dyspepsia at the same institution. Control participants were matched to patients with Wilson's disease by age and sex. All participants were recruited from the same hospital setting during the study period.
Who may be able to join
- Wilson's Disease Group:
- Adult patients (≥18 years) diagnosed with Wilson's disease
- Followed at gastroenterology and/or neurology clinics
- Clinically stable at the time of study inclusion
- Provided written informed consent
- Control Group:
Show all 10Show fewer
- Adult patients (≥18 years) with dyspepsia
- No known diagnosis of Wilson's disease or other disorders of copper metabolism
- Age- and sex-matched to patients with Wilson's disease
- Provided written informed consent
Who cannot join
- (Applied to both groups unless otherwise specified)
- Acute liver-related disease or complications, including:
- Acute liver failure
- Acute-on-chronic liver failure
- Spontaneous bacterial peritonitis
- Hepatic encephalopathy
Show all 9Show fewer
- Hepatorenal syndrome
- Presence of diseases affecting copper metabolism other than Wilson's disease, including: Menkes disease, Malnutrition, Malabsorption syndromes
- Inability or unwillingness to provide informed consent
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Hacettepe Üniversitesi İç Hastalıkları Anabilim Dalı
Ankara, Sıhhıye, 06100
About this study
Official title: Comparison of Serum Exchangeable and Relative Exchangeable Copper Levels With Clinical Parameters and Multiparametric Liver MRI Findings in Patients With Wilson's Disease
Serum exchangeable copper (EC) and relative exchangeable copper (REC) are blood tests developed to improve the assessment of copper levels in patients with Wilson's disease. EC measures the fraction of copper in the blood that is not bound to ceruloplasmin and reflects copper accumulation in the body. REC represents the proportion of this exchangeable copper relative to total serum copper. Previous studies have shown that EC and REC are more accurate than traditional copper tests for diagnosing Wilson's disease. This study aimed to evaluate the relationship between EC/REC and routine copper measurements in patients with Wilson's disease during follow-up, to assess their potential value in disease monitoring.
Read the detailed description
Wilson's disease (WD) is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene and transmitted in an autosomal recessive manner. The disease leads to progressive copper accumulation in multiple organs, particularly the liver and brain, resulting in a wide spectrum of clinical manifestations, including hepatic, neurological, and psychiatric involvement.
Accurate monitoring of copper levels is essential for evaluating treatment response and adjusting therapy in patients with WD. In routine clinical practice, copper status is commonly assessed using 24-hour urinary copper excretion and non-ceruloplasmin-bound copper. However, these traditional measurements have important limitations. Collection of 24-hour urine samples is cumbersome and prone to errors, and interpretation may be challenging in patients with renal dysfunction or neurological involvement.
Total serum copper reflects both ceruloplasmin-bound and non-ceruloplasmin-bound copper. In WD, despite increased total body copper, serum ceruloplasmin levels are reduced, leading to low ceruloplasmin-bound copper concentrations. As a result, total serum copper measurements may not reliably reflect copper overload. Non-ceruloplasmin-bound copper is calculated indirectly by subtracting ceruloplasmin-bound copper from total serum copper and depends on accurate ceruloplasmin measurement. Immunological assays may overestimate ceruloplasmin levels, resulting in unreliable or even negative calculated values.
Serum exchangeable copper (EC) and relative exchangeable copper (REC) have been developed to address these limitations. EC represents the directly measured fraction of serum copper that is not bound to ceruloplasmin and is thought to better reflect bioavailable and tissue copper accumulation. REC is calculated as the ratio of EC to total serum copper. Previous studies have shown that EC and REC are more sensitive and specific than conventional copper tests and have been validated for the diagnosis of WD. However, their role as biomarkers in the follow-up and management of patients with WD has not been fully established.
The aim of this study was to evaluate the relationship between EC and REC and routine copper measurements in adult patients with Wilson's disease during follow-up, in order to assess their potential utility in monitoring copper status.
- Conditions
- Wilson's Disease
- Keywords
- Wilson's disease, Serum Exhangeable Copper, Relative Exchangeable Copper, Total Serum Copper, 24 hour urinary copper excretion
- 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 |
|---|---|---|
| Wilson's Disease Patients | Adult patients diagnosed with Wilson's disease who were followed at gastroenterology and neurology clinics. Participants underwent clinical evaluation and routine laboratory assessments, including serum exchangeable copper, relative exchangeable copper, total serum copper, and 24-hour urinary copper excretion. No study-specific intervention was assigned. | |
| Control Group | Age- and sex-matched control participants with dyspepsia and no known disorders of copper metabolism. Participants underwent serum exchangeable copper, total serum copper, and routine blood tests. No urine samples were collected and no study-specific intervention was assigned. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation Between Serum Exchangeable Copper and 24-hour Urinary Copper Excretion in Wilson's Disease
Correlation coefficient (r) between serum exchangeable copper (EC) concentration (µmol/L), measured by inductively coupled plasma mass spectrometry (ICP-MS), and 24-hour urinary copper excretion (µg/24 h), measured by atomic absorption spectrometry, in adult patients with Wilson's disease
Measured: Day 1
Correlation Between Serum Exchangeable Copper and Total Serum Copper in Wilson's Disease and Controls
Correlation coefficient (r) between serum exchangeable copper (EC) concentration (µmol/L) and total serum copper concentration (µmol/L), both measured by inductively coupled plasma mass spectrometry (ICP-MS), in adult patients with Wilson's disease and age- and sex-matched control participants
Measured: Day 1
Assessment of Correlation Between Relative Exchangeable Copper and Urinary Copper Excretion in Wilson's Disease
Correlation coefficient (r) between relative exchangeable copper (REC, %) and 24-hour urinary copper excretion (µg/24 h), measured by atomic absorption spectrometry, in adult patients with Wilson's disease
Measured: Day 1
Secondary outcomes (13)
Difference in serum exchangeable copper (EC) between Wilson's disease patients and controls
Comparison of serum exchangeable copper (EC) levels between adult patients with Wilson's disease and age- and sex-matched control participants.
Measured: Day 1
Difference in relative exchangeable copper (REC) between Wilson's disease patients and controls
Comparison of relative exchangeable copper (REC) levels between adult patients with Wilson's disease and age- and sex-matched control participants.
Measured: Day 1
Difference in total serum copper between Wilson's disease patients and controls
Comparison of total serum copper levels between adult patients with Wilson's disease and age- and sex-matched control participants.
Measured: Day 1
Comparison of 24-hour urinary copper excretion by Disease Phenotype in Wilson's Disease
Comparison of 24-hour urinary copper excretion (µg/day) between adult patients with hepatic involvement and those with hepatic-neurologic involvement in Wilson's disease.
Measured: Day 1
Comparison of Serum Exchangeable Copper by Disease Phenotype in Wilson's Disease
Comparison of serum exchangeable copper (EC, µmol/L) between patients with hepatic involvement and those with hepatic-neurologic involvement, in adult patients with Wilson's disease.
Measured: Day 1
Comparison of Relative Exchangeable Copper by Disease Phenotype in Wilson's Disease
Comparison of relative exchangeable copper (REC, %), between patients with hepatic involvement and those with hepatic-neurologic involvement, in adult patients with Wilson's disease.
Measured: Day 1
Comparison of Total Serum Copper by Disease Phenotype in Wilson's Disease
Comparison of total serum copper concentration (µmol/L), between patients with hepatic involvement and those with hepatic-neurologic involvement, in adult patients with Wilson's disease.
Measured: Day 1
Comparison of Copper Tests by Chelator Treatment in Wilson's Disease
Differences in 24-hour urinary copper excretion (µg/day), serum exchangeable copper (EC, µmol/L), relative exchangeable copper (REC, %), and total serum copper concentration (µmol/L) between patients treated with penicillamine and those treated with trientine, in adult patients with Wilson's disease
Measured: Day 1
Correlation of 24-Hour Urinary Copper Excretion With Ceruloplasmin and Routine Laboratory Parameters in Wilson's Disease
Correlation coefficient (r) between 24-hour urinary copper excretion (µg/day) and serum ceruloplasmin levels and selected routine laboratory parameters (including liver enzymes, bilirubin, albumin, and blood cell counts) in adult patients with Wilson's disease.
Measured: Day 1
Correlation of Serum Exchangeable Copper With Ceruloplasmin and Routine Laboratory Parameters in Wilson Disease
Correlation coefficient (r) between serum exchangeable copper (EC, µmol/L) and serum ceruloplasmin levels and selected routine laboratory parameters (including liver enzymes, bilirubin, albumin, and blood cell counts) in adult patients with Wilson's disease.
Measured: Day 1
Correlation of Relative Exchangeable Copper With Ceruloplasmin and Routine Laboratory Parameters in Wilson Disease
Correlation coefficient (r) between relative exchangeable copper (REC, %) and serum ceruloplasmin levels and selected routine laboratory parameters (including liver enzymes, bilirubin, albumin, and blood cell counts) in adult patients with Wilson's disease.
Measured: Day 1
Correlation of Total Serum Copper Concentration With Ceruloplasmin and Routine Laboratory Parameters in Wilson Disease
Correlation coefficient (r) between total serum copper concentration (µmol/L) and serum ceruloplasmin levels and selected routine laboratory parameters (including liver enzymes, bilirubin, albumin, and blood cell counts) in adult patients with Wilson's disease.
Measured: Day 1
Distribution of Urinary Copper Excretion Categories in Wilson's Disease
Proportion of adult patients with Wilson's disease classified as having low, on-target, or high 24-hour urinary copper excretion according to treatment-specific target ranges
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start31 Jan 2021
- Primary completion5 Sep 2021
- Study completion5 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wilson's DiseaseStudies of the same condition, open and under way.
- More trials run by Hacettepe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 81 participants (actual)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Hacettepe University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bekir Mert Durukan, Hacettepe University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07462026
- Sponsor's protocol ID
- 16969557-29
- Status last verified
- Mar 2026
- First submitted
- 15 Feb 2026
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared due to ethical and privacy considerations and because informed consent did not include permission for data sharing beyond the scope of the current study.
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Serum Exchangeable and Relative Exchangeable Copper Levels With Clinical Parameters and Multiparametric Liver MRI Findings in Patients With Wilson's Disease
- ClinicalTrials.gov ID
- NCT07462026
- Acronym / sponsor ID
- 16969557-29
- Conditions
- Wilson's Disease
- Keywords
- Wilson's disease, Serum Exhangeable Copper, Relative Exchangeable Copper, Total Serum Copper, 24 hour urinary copper excretion
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Hacettepe UniversityUniversity, hospital or other
- Study start
- 31 Jan 2021 (actual)
- Primary completion
- 5 Sep 2021 (actual)
- Study completion
- 5 Sep 2021 (actual)
- First posted
- 10 Mar 2026 (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.
Serum exchangeable copper (EC) and relative exchangeable copper (REC) are blood tests developed to improve the assessment of copper levels in patients with Wilson's disease. EC measures the fraction of copper in the blood that is not bound to ceruloplasmin and reflects copper accumulation in the body. REC represents the proportion of this exchangeable copper relative to total serum copper. Previous studies have shown that EC and REC are more accurate than traditional copper tests for diagnosing Wilson's disease. This study aimed to evaluate the relationship between EC/REC and routine copper measurements in patients with Wilson's disease during follow-up, to assess their potential value in disease monitoring.
Detailed description
Wilson's disease (WD) is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene and transmitted in an autosomal recessive manner. The disease leads to progressive copper accumulation in multiple organs, particularly the liver and brain, resulting in a wide spectrum of clinical manifestations, including hepatic, neurological, and psychiatric involvement.
Accurate monitoring of copper levels is essential for evaluating treatment response and adjusting therapy in patients with WD. In routine clinical practice, copper status is commonly assessed using 24-hour urinary copper excretion and non-ceruloplasmin-bound copper. However, these traditional measurements have important limitations. Collection of 24-hour urine samples is cumbersome and prone to errors, and interpretation may be challenging in patients with renal dysfunction or neurological involvement.
Total serum copper reflects both ceruloplasmin-bound and non-ceruloplasmin-bound copper. In WD, despite increased total body copper, serum ceruloplasmin levels are reduced, leading to low ceruloplasmin-bound copper concentrations. As a result, total serum copper measurements may not reliably reflect copper overload. Non-ceruloplasmin-bound copper is calculated indirectly by subtracting ceruloplasmin-bound copper from total serum copper and depends on accurate ceruloplasmin measurement. Immunological assays may overestimate ceruloplasmin levels, resulting in unreliable or even negative calculated values.
Serum exchangeable copper (EC) and relative exchangeable copper (REC) have been developed to address these limitations. EC represents the directly measured fraction of serum copper that is not bound to ceruloplasmin and is thought to better reflect bioavailable and tissue copper accumulation. REC is calculated as the ratio of EC to total serum copper. Previous studies have shown that EC and REC are more sensitive and specific than conventional copper tests and have been validated for the diagnosis of WD. However, their role as biomarkers in the follow-up and management of patients with WD has not been fully established.
The aim of this study was to evaluate the relationship between EC and REC and routine copper measurements in adult patients with Wilson's disease during follow-up, in order to assess their potential utility in monitoring copper status.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Wilson's Disease Patients | – | –Adult patients diagnosed with Wilson's disease who were followed at gastroenterology and neurology clinics. Participants underwent clinical evaluation and routine laboratory assessments, including serum exchangeable copper, relative exchangeable copper, total serum copper, and 24-hour urinary copper excretion. No study-specific intervention was assigned. |
| Control Group | – | –Age- and sex-matched control participants with dyspepsia and no known disorders of copper metabolism. Participants underwent serum exchangeable copper, total serum copper, and routine blood tests. No urine samples were collected and no study-specific intervention was assigned. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population consisted of adult patients with Wilson's disease who were followed at the gastroenterology and neurology outpatient clinics of a tertiary university hospital. A control population was selected from adult patients presenting with dyspepsia at the same institution. Control participants were matched to patients with Wilson's disease by age and sex. All participants were recruited from the same hospital setting during the study period.
Key inclusion criteria (10 listed)
- Adult patients (≥18 years) diagnosed with Wilson's disease
- Followed at gastroenterology and/or neurology clinics
- Clinically stable at the time of study inclusion
- Provided written informed consent
- Adult patients (≥18 years) with dyspepsia
Key exclusion criteria (9 listed)
- (Applied to both groups unless otherwise specified)
- Acute liver-related disease or complications, including:
- Acute liver failure
- Acute-on-chronic liver failure
- Spontaneous bacterial peritonitis
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
Correlation Between Serum Exchangeable Copper and 24-hour Urinary Copper Excretion in Wilson's Disease
Time frame: Day 1
Correlation coefficient (r) between serum exchangeable copper (EC) concentration (µmol/L), measured by inductively coupled plasma mass spectrometry (ICP-MS), and 24-hour urinary copper excretion (µg/24 h), measured by atomic absorption spectrometry, in adult patients with Wilson's disease
Correlation Between Serum Exchangeable Copper and Total Serum Copper in Wilson's Disease and Controls
Time frame: Day 1
Correlation coefficient (r) between serum exchangeable copper (EC) concentration (µmol/L) and total serum copper concentration (µmol/L), both measured by inductively coupled plasma mass spectrometry (ICP-MS), in adult patients with Wilson's disease and age- and sex-matched control participants
Assessment of Correlation Between Relative Exchangeable Copper and Urinary Copper Excretion in Wilson's Disease
Time frame: Day 1
Correlation coefficient (r) between relative exchangeable copper (REC, %) and 24-hour urinary copper excretion (µg/24 h), measured by atomic absorption spectrometry, in adult patients with Wilson's disease
13 secondary outcomes
Difference in serum exchangeable copper (EC) between Wilson's disease patients and controls
Time frame: Day 1
Difference in relative exchangeable copper (REC) between Wilson's disease patients and controls
Time frame: Day 1
Difference in total serum copper between Wilson's disease patients and controls
Time frame: Day 1
Comparison of 24-hour urinary copper excretion by Disease Phenotype in Wilson's Disease
Time frame: Day 1
Comparison of Serum Exchangeable Copper by Disease Phenotype in Wilson's Disease
Time frame: Day 1
Comparison of Relative Exchangeable Copper by Disease Phenotype in Wilson's Disease
Time frame: Day 1
Comparison of Total Serum Copper by Disease Phenotype in Wilson's Disease
Time frame: Day 1
Comparison of Copper Tests by Chelator Treatment in Wilson's Disease
Time frame: Day 1
Correlation of 24-Hour Urinary Copper Excretion With Ceruloplasmin and Routine Laboratory Parameters in Wilson's Disease
Time frame: Day 1
Correlation of Serum Exchangeable Copper With Ceruloplasmin and Routine Laboratory Parameters in Wilson Disease
Time frame: Day 1
Correlation of Relative Exchangeable Copper With Ceruloplasmin and Routine Laboratory Parameters in Wilson Disease
Time frame: Day 1
Correlation of Total Serum Copper Concentration With Ceruloplasmin and Routine Laboratory Parameters in Wilson Disease
Time frame: Day 1
Distribution of Urinary Copper Excretion Categories in Wilson's Disease
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared due to ethical and privacy considerations and because informed consent did not include permission for data sharing beyond the scope of the current study.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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's Disease, run by Hacettepe University at 1 site in Turkey (Türkiye).
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 10 inclusion and 9 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: finished, as of the sponsor's last update on 10 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 Turkey (Türkiye). 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation Between Serum Exchangeable Copper and 24-hour Urinary Copper Excretion in Wilson's Disease (time frame: Day 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Mar 2026.