The Individual Therapy for Patients With Wilson's Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Wilson's Disease
• Intervention / Treatment: Drug: DMPS; Drug: DMSA; Drug: Penicillamine; Drug: Zinc gluconate

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 Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zhi-Ying Wu, MD&PhD; Phone Number: +86-571-87783569; Email: zhiyingwu@zju.edu.cn
• Study Contact Backup: Name: Yi Dong, MD&PhD; Phone Number: +8618367129345; Email: dongyi720@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • econd Affiliated Hospital,Zhejiang University School of Medicine
      • Contact: Zhi-Ying Wu, MD&PhD; Phone Number: +86-571-87783569; Email: zhiyingwu@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: homo-R778L; 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; Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; Other Names: Sodium Dimercaptosulphonate; Drug: DMSA; 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; Other Names: Dimercaptosuccinic Acid
Experimental: R778L+truncation mutation; 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; Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; Other Names: Sodium Dimercaptosulphonate; Drug: DMSA; 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; Other Names: Dimercaptosuccinic Acid
Experimental: Homo-P992L; 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; Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; Other Names: Sodium Dimercaptosulphonate; Drug: DMSA; 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; Other Names: Dimercaptosuccinic Acid
Experimental: P992L+truncation mutation; 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; Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; Other Names: Sodium Dimercaptosulphonate; Drug: DMSA; 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; Other Names: Dimercaptosuccinic Acid
Experimental: T935M+other point mutations; 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; Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days; Other Names: Sodium Dimercaptosulphonate; Drug: DMSA; 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; Other Names: Dimercaptosuccinic Acid; Drug: Penicillamine; Dosage Form: Penicillamine: 250-1500mg per day, Frequency:TID,Duration: 5 years;
Experimental: Presymptomatic patients with Wilson's disease; 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; 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;

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Zhi-Ying Wu, MD&PhD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: May 19, 2019
• First Posted (Actual): May 21, 2019

Study Record Updates

• Last Update Posted (Actual): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 19, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Metal Metabolism, Inborn Errors; Hepatolenticular Degeneration; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Protective Agents; Antidotes; Chelating Agents; Sequestering Agents; Succimer; Penicillamine
• Other Study ID Numbers: WuZYLab-WD

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