| Hepatic Endpoints |
The clinical important hepatological endpoints include fibrosis progression and development of cirrhosis and its complications (ascites, esophageal varices, jaundice, and HE). No measure has been validated as a hepatological surrogate endpoint, but the likely candidate is fibrosis progression/regression assessed by transient elastography or MRE. Surrogate markers should include clinical scores in cirrhosis (MELD, Child‐Pugh). Exploratory endpoints may include peripheral fibrosis markers (FIB‐4 index, APRI, and ELF), markers of inflammation, and quantitative liver function tests (galactose elimination capacity, LiMax test, or lidocaine clearance test). Exploratory endpoints also include ALT, AST, and other liver function tests to monitor treatment safety.
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| Identified areas of research |
| High priority |
Prospective validation in large cohorts of WD patients of transient elastography (FibroScan, ARFI, or MRE) as possible surrogate markers for fibrosis regression/progression and development of cirrhosis in the individual patient
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| Others |
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| Neurological endpoints |
The use of a common neurological rating scale will facilitate comparison between studies and is recommended. At the present time, the panel recommends the use of the UWDRS as an important neurological endpoint. No measure has been validated as a neurological surrogate endpoint or surrogate marker. Exploratory endpoints may include MRI, evoked potentials, psychiatric disease, and the use of drugs to treat psychiatric disease.
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| Identified areas of research |
| High priority |
Development of a neurological score that is less complex and with good correlation to the physical well‐being of the patient Prospective validation in large cohorts of WD patients whether changes on MRI described in a reproducible way parallel clinical neurological development in the individual patient Development of specific measures to evaluate psychiatric disease as well as quality of life in WD patients
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| Others |
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| Endpoints related to assessment of copper metabolism |
No measure of copper metabolism has been validated as a surrogate endpoint. The most likely candidates are NCC, CuEXC, and 24‐hour urine copper after a 48‐hour drug holiday. The 24‐hour urine excretion on current treatment or after a 48‐hour drug holiday may be included as a surrogate marker. Exploratory endpoints may include optical coherence tomographic assessment of KF ring intensity.
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| Identified areas of research |
| High priority |
Prospective validation in large cohorts of treated WD patients as to whether NCC, CuEXC, or 24‐hour urinary copper after a 48‐hour drug holiday are predictive of important clinical endpoints Development and validation of methods to quantify plasma copper that is bioavailable
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| Others |
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