Circadian Variation of Urinary Copper Excretion in Wilson Disease Patients (VARCUWIC)

Circadian Variation of Urinary Copper Excretion in Wilson Disease Patients Treated With Chelators or Zinc Salts

Wilson's disease (WD) is a genetic disorder characterized by an accumulation of copper in the body, mainly in the liver and brain. Patients suffering from this disease are monitored by liver function tests, blood copper levels, and 24-hour urinary copper determinations.

Treatment is based either on chelating the copper accumulated in the body using D-penicillamine or Trientine or on limiting intestinal copper absorption with zinc salts.

Monitoring copper elimination in urine collected over 24 hours is essential for estimating a patient's copper load, adapting treatment dosage, and detecting any copper deficiency.

Nevertheless, urine collection is often complicated for patients, given the obvious constraints of collecting urine over 24 hours. Without this, clinical decisions are usually made based on spot urine.

There is no official recommendation for monitoring urinary copper elimination other than on 24-hour urine.

According to studies on healthy volunteers under physiological conditions, urinary copper elimination occurs according to a circadian rhythm, with minimal copper elimination between 8 pm and 4 am and maximum between 8 am and noon.

The study would aim to find the period of the day best correlated with 24h urinary copper excretion

Study Overview

• Status: Recruiting
• Conditions: Wilson Disease
• Intervention / Treatment: Diagnostic test: urine and blood test

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Eduardo Couchonnal, Dr; Phone Number: +33 04 27 35 70 50; Email: eduardo.couchonnal-bedoya@chu-lyon.fr
• Study Contact Backup: Name: Abdelouahed BELMALIH, PhD; Phone Number: +33 04 27 85 62 67; Email: abdelouahed.belmalih@chu-lyon.fr

Study Locations

• France
  • Rhone
    • Bron, Rhone, France, 69500
      • Recruiting
      • Service de Gastroentérologie, Hépatologie et Nutrition Pédiatriques - Hôpital Femme Mère Enfant
      • Contact: Eduardo Couchonnal, Dr; Phone Number: +33 04 27 35 70 50; Email: eduardo.couchonnal-bedoya@chu-lyon.fr
      • Contact: Abdelouahed BELMALIH, PhD; Phone Number: +33 04 27 85 62 67; Email: abdelouahed.belmalih@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

- Patients with a confirmed diagnosis of Wilson's Disease (Leipzig score ˃4).

Description

Inclusion Criteria:

• Patients with a confirmed diagnosis of Wilson's Disease (Leipzig score ˃4).
• Age ≥ 6 years and ≤70 years.
• Patient able to perform 24h urine.
• Current treatment with D-Pencillamine, Trientine or Zinc.
• Non-opposition of patient and/or legal representatives for minor patients.

Exclusion Criteria:

• Patients who had a change in treatment within the last 6 months before the inclusion
• Patients who have undergone liver transplantation
• Patients with known chronic renal failure (GFR < 30 ml/min)
• Patients on long-term diuretic or corticosteroid therapy
• Persons deprived of liberty by a judicial or administrative decision
• Patient under judicial protection, unable to express consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1 - DP; Patients with a confirmed diagnosis of Wilson's Disease (Leipzig score ˃4 ). Aged between 6 years and 70 years. Treated with D-Pencillamine	Diagnostic test: urine and blood test; 3 urine collections of an 8h period. One blood sample for liver function test and copper assessment
Group 2 - Trientine; Patients with a confirmed diagnosis of Wilson's Disease (Leipzig score ˃4 ). Aged between 6 years and 70 years. Treated with Trientine	Diagnostic test: urine and blood test; 3 urine collections of an 8h period. One blood sample for liver function test and copper assessment
Group 3 - ZINC; Patients with a confirmed diagnosis of Wilson's Disease (Leipzig score ˃4 ). Aged between 6 years and 70 years. Treated with Zinc.	Diagnostic test: urine and blood test; 3 urine collections of an 8h period. One blood sample for liver function test and copper assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation factor	Correlation between 24-hour urinary copper excretion and 8-hour urinary copper excretion collected between midnight and 8 am).	Two 24-hour urine recollection

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2025
• Primary Completion (Estimated): February 10, 2027
• Study Completion (Estimated): February 10, 2027

Study Registration Dates

• First Submitted: May 21, 2024
• First Submitted That Met QC Criteria: May 21, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Wilson disease; chelator; urinary copper
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Neurodegenerative Diseases; Liver Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metal Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hepatolenticular Degeneration; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Reproductive and Urinary Physiological Phenomena; Urinary Tract Physiological Phenomena; Hematologic Tests; Urination
• Other Study ID Numbers: 69HCL23_1227

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No