The Individual Therapy for Patients With Wilson's Disease

Study Overview
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Brief Summary
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Based on the genotype characteristics and genotype-phenotype-treatment prognosis data of Chinese WD patients, this study intends to further optimize the treatment regimen of Chinese WD patients and formulate individualized treatment regimens for each genotype, so as to further improve the prognosis of patients.

Detailed Description
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The purpose of the study is to evaluate treatment regimen efficacy based on different mutations, and Zinc treatment in presymptomatic WD patients.

Official Title
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The Individual Therapy for Patients With Wilson's Disease

Conditions
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Wilson's Disease

Intervention / Treatment
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* Drug: DMPS
* Drug: Penicillamine
* Drug: DMSA
* Drug: Zinc gluconate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetic diagnosis of Wilson's disease Presymptomatic patients with Wilson's disease Exclusion Criteria: Movement disorder due to other definite causes instead of Wilson's disease Severe Lung, kidney or liver disease Neoplastic Disease
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: homo-R778L<br>When patients carrying homo-R778L mutation are in hospital, they receive DMPS treatment. Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; When being off hospital, they receive DMSA treatment. Adult patient,Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Pediatric patient,Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years; | Drug: DMPS<br>* Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days;<br>* Other names: Sodium Dimercaptosulphonate;Drug: DMSA<br>* Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years;<br>* Other names: Dimercaptosuccinic Acid;|
| Experimental: R778L+truncation mutation<br>When patients carrying R778L and truncation mutation are in hospital, they receive DMPS treatment. Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; When being off hospital, they receive DMSA treatment. Adult patient,Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Pediatric patient ,Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years; | Drug: DMPS<br>* Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days;<br>* Other names: Sodium Dimercaptosulphonate;Drug: DMSA<br>* Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years;<br>* Other names: Dimercaptosuccinic Acid;|
| Experimental: Homo-P992L<br>When patients carrying Homo-P992L mutation are in hospital, they receive DMPS treatment. Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; When being off hospital, they receive DMSA treatment. Adult patient,Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Pediatric patient ,Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years; | Drug: DMPS<br>* Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days;<br>* Other names: Sodium Dimercaptosulphonate;Drug: DMSA<br>* Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years;<br>* Other names: Dimercaptosuccinic Acid;|
| Experimental: P992L+truncation mutation<br>When patients carrying P992L and truncation mutation are in hospital, they receive DMPS treatment. Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; When being off hospital, they receive DMSA treatment. Adult patient,Dosage Form:DMSA:750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Pediatric patient,Dosage Form:DMSA:35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years; | Drug: DMPS<br>* Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days;<br>* Other names: Sodium Dimercaptosulphonate;Drug: DMSA<br>* Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years;<br>* Other names: Dimercaptosuccinic Acid;|
| Experimental: T935M+other point mutations<br>When patients carrying T935M and other point mutations are in hospital, they randomly receive DMPS or penicillamine treatment; Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; Dosage Form: penicillamine: 250-1500mg per day, Frequency:TID,Duration: 5 years; When being off hospital, they receive DMSA treatment or penicillamine. Adult patient,Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Pediatric patient,Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years; | Drug: DMPS<br>* Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days;<br>* Other names: Sodium Dimercaptosulphonate;Drug: Penicillamine<br>* Dosage Form: Penicillamine: 250-1500mg per day, Frequency:TID,Duration: 5 years;<br>Drug: DMSA<br>* Dosage Form: DMSA: 750-1000mg per day,DMSA Frequency:BID,DMSA Duration: 5 years; Dosage Form: DMSA: 35mg/kg per day,DMSA Frequency:BID,DMSA Duration: 5 years;<br>* Other names: Dimercaptosuccinic Acid;|
| Experimental: Presymptomatic patients with Wilson's disease<br>According to different age group, they receive various dosage of Zinc Gluconate treatment. Patient aged≤6 years,Dosage Form: Zinc Gluconate: 140mg once, Zinc Gluconate Frequency:BID, Zinc Gluconate Duration: 5 years; Patient aged from 6 to 14 years,Dosage Form: Zinc Gluconate: 140mg once, Zinc Gluconate Frequency:TID, Zinc Gluconate Duration: 5 years; Patient aged≥14 years,Dosage Form: Zinc Gluconate: 210mg once, Zinc Gluconate Frequency:TID, Zinc Gluconate Duration: 5 years; | Drug: Zinc gluconate<br>* Dosage Form: Zinc gluconate: 140mg per time,Zinc Frequency:BID,Zinc Duration: 5 years; Dosage Form: Zinc gluconate: 140mg per time,Zinc Frequency:TID,Zinc Duration: 5 years; Dosage Form: Zinc gluconate: 210mg per time,Zinc Frequency:TID,Zinc Duration: 5 years;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum ceruloplasmin | Serum ceruloplasmin concentration will be analysed using a validated assay | Five years | 
| 24-hour urine copper | 24-hour urinary copper excretion is to be measured | Five years | 
| serum copper | serum copper will be analysed using a validated assay | Five years | 
| White blood cell | The white blood cell will be evaluated using a validated assay | Five years | 
| Platelet count | The platelet count will be evaluated using a validated assay | Five years | 
| urine protein level | The urine protein level will be collected using a validated assay | Five years | 
| Alanine transaminase | The concentration of alanine transaminase will be collected using a validated assay | Five years | 
| blood creatinine | The concentration of blood creatinine will be tested using a validated assay | Five years | 
| international normalized ratio | The international normalized ratio will be analyzed | Five years | 
| hepatic fibrosis markers test | The concentrations of procollagen III, collage IV and hyaluronidase will be evaluated using a validated assay | Five years | 
| bone mineral density test | The bone mineral density will be tested using the dual energy X ray absorptiometry | Five years | 
| Abdominal ultrasound | The abdominal ultrasound will be collected | Five years | 
| Urinary ultrasound | The urinary ultrasound will be analyzed in patients | Five years | 
| Cranial MRI scan | The cranial MRI scan will be analyzed in patients | Five years | 
| Unified Wilson's disease rating scale | The Unified Wilson's disease rating scale consist of three subscales, including neurological part (0 112), liver functional part (0 36) and mental state part (0 76). Three subscale scores are summed to compute a total score. The higher values represent a worse outcome | Five years |