Early Detection of Cardiac Affection in Patients of Wilson's Disease (Wilson's)

• ClinicalTrials.gov Identifier: NCT06051734
• Recruitment Status: Not yet recruiting
• First Posted: September 25, 2023
• Last Update Posted: September 25, 2023
• Sponsor: Assiut University
• Information provided by (Responsible Party): Salma Taha, Assiut University

Study Description

Brief Summary:

Wilson disease (WD) is a rare autosomal recessive disorder caused by a genetic defect in ATP7B resulting in limited excretion of excess copper into the bile Pathological copper accumulation occurs in the entire body, with the liver and the brain being primarily affected

Condition or disease
Cardiovascular Diseases; Wilson's Disease

Detailed Description:

Wilson disease (WD) is a rare autosomal recessive disorder caused by a genetic defect in ATP7B resulting in limited excretion of excess copper into the bile. Pathological copper accumulation occurs in the entire body, with the liver and the brain being primarily affected. The pathological copper accumulation may induce toxic injury, including mitochondrial dysfunction or apoptosis . Exhausted hepatic copper storage capacity causes copper release into the bloodstream thus affecting other organs, in particular the brain. The neurotoxicity of copper primarily damages astrocytes, leading to a regional destruction of the blood-brain barrier with subsequent neurological symptoms. Asymptomatic cardiac arrhythmias are quite common in WD. Cardiomyopathy, autonomic dysfunction, and cardiac deaths due to copper accumulation in cardiac tissue have occasionally been reported in WD. Copper accumulation induces toxic effects in cardiomyocytes and the clinical consequences of these myocardial accumulations are poorly understood. Previous studies have mainly reported mild cardiac abnormalities including concentric hypertrophy, impaired left ventricular (LV) relaxation and minor electrocardiographic changes, mainly reported in the times before appropriate treatment was available. A longitudinal cohort study demonstrated a higher incidence of heart failure (HF) and atrial fibrillation in WD patients, indicating a potential adverse effect of copper on the heart. Cardiovascular magnetic resonance (CMR) allows for a non-invasive tissue characterization, specifically visualizing edema, fibrosis, and pathological infiltrations. CMR has been successfully used for diagnosis and therapy monitoring in other storage diseases such as myocardial iron overload and amyloidosis. Survival in patients with thalassemia major improved significantly after the introduction of CMR for identifying myocardial iron accumulation. Imaging regional fibrosis using CMR late gadolinium enhancement (LGE) and quantitative measurement of extracellular volume (ECV) provide independent prognostic markers in cardiac amyloidosis.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 50 participants
• Observational Model: Case-Crossover
• Time Perspective: Prospective
• Target Follow-Up Duration: 5 Years
• Official Title: Early Detection of Cardiac Affection in Patients of Wilson's Disease
• Estimated Study Start Date: October 1, 2023
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: September 30, 2029

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. evaluate spectrum of cardiac affection by copper deposition in Wilson disease patients and detect early cardiac affection [ Time Frame: 1 year ]
   Evaluate the effect of copper on EF and diastolic function of LV and RV

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

All patients with Wilson's disease attending outpatient clinic

Criteria

Inclusion Criteria:

• All patients diagnosed with Wilson's

Exclusion Criteria:

• Claustrophobia
• Refusal to share information
• Heart failure

Contacts and Locations

Contacts

Contact: Salma Taha, Ass.Professor; +201003329108; esmaeil.salma@gmail.com

Sponsors and Collaborators

Assiut University

More Information

• Responsible Party: Salma Taha, Ass.Prof., Assiut University
• ClinicalTrials.gov Identifier: NCT06051734
• Other Study ID Numbers: Assiut University and Liver; Wilson's and heart ( Registry Identifier: Wilson's and cardiac affection )
• First Posted: September 25, 2023
• Last Update Posted: September 25, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Salma Taha, Assiut University:

Wilson's; CMR; Cardiac magnetic resonance

Additional relevant MeSH terms:

Hepatolenticular Degeneration; Cardiovascular Diseases; 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; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases