The Individual Therapy for Patients With Wilson's Disease

Early Phase 1

Recruiting

• Conditions: Wilson's Disease
• Interventions: Drug: Zinc gluconate; Drug: DMPS; Drug: DMSA; Drug: Penicillamine

• Registration Number: NCT03957720
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

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

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

Study Timeline

• Study Start: 2019-03-15
• Study First Submitted: 2019-04-08
• Status Verified: 2019-05
• Study First Submitted QC: 2019-05-19
• Last Update Submitted: 2019-05-19
• Study First Posted: 2019-05-21
• Last Update Posted: 2019-05-21
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
homo-R778L	DMSA	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;
R778L+truncation mutation	DMSA	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;
Homo-P992L	DMSA	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;
P992L+truncation mutation	DMSA	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;
T935M+other point mutations	Penicillamine	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;
T935M+other point mutations	DMSA	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;
Presymptomatic patients with Wilson's disease	Zinc gluconate	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;
homo-R778L	DMPS	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;
R778L+truncation mutation	DMPS	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;
Homo-P992L	DMPS	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;
P992L+truncation mutation	DMPS	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;
T935M+other point mutations	DMPS	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;

Primary Outcome Measures

Name	Time	Method
Serum ceruloplasmin	Five years	Serum ceruloplasmin concentration will be analysed using a validated assay
24-hour urine copper	Five years	24-hour urinary copper excretion is to be measured
serum copper	Five years	serum copper will be analysed using a validated assay
White blood cell	Five years	The white blood cell will be evaluated using a validated assay
Platelet count	Five years	The platelet count will be evaluated using a validated assay
urine protein level	Five years	The urine protein level will be collected using a validated assay
Alanine transaminase	Five years	The concentration of alanine transaminase will be collected using a validated assay
blood creatinine	Five years	The concentration of blood creatinine will be tested using a validated assay
international normalized ratio	Five years	The international normalized ratio will be analyzed
hepatic fibrosis markers test	Five years	The concentrations of procollagen III, collage IV and hyaluronidase will be evaluated using a validated assay
bone mineral density test	Five years	The bone mineral density will be tested using the dual energy X ray absorptiometry
Abdominal ultrasound	Five years	The abdominal ultrasound will be collected
Urinary ultrasound	Five years	The urinary ultrasound will be analyzed in patients
Cranial MRI scan	Five years	The cranial MRI scan will be analyzed in patients
Unified Wilson's disease rating scale	Five years	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

Trial Locations

Locations (1)

econd Affiliated Hospital,Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China