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The Individual Therapy for Patients With Wilson's Disease

Primary Purpose

Wilson's Disease

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
DMPS
Penicillamine
DMSA
Zinc gluconate
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wilson's Disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • econd Affiliated Hospital,Zhejiang University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

homo-R778L

R778L+truncation mutation

Homo-P992L

P992L+truncation mutation

T935M+other point mutations

Presymptomatic patients with Wilson's disease

Arm Description

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;

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;

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;

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;

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;

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;

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
April 8, 2019
Last Updated
May 19, 2019
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT03957720
Brief Title
The Individual Therapy for Patients With Wilson's Disease
Official Title
The Individual Therapy for Patients With Wilson's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2019 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wilson's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
homo-R778L
Arm Type
Experimental
Arm Description
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;
Arm Title
R778L+truncation mutation
Arm Type
Experimental
Arm Description
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;
Arm Title
Homo-P992L
Arm Type
Experimental
Arm Description
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;
Arm Title
P992L+truncation mutation
Arm Type
Experimental
Arm Description
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;
Arm Title
T935M+other point mutations
Arm Type
Experimental
Arm Description
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;
Arm Title
Presymptomatic patients with Wilson's disease
Arm Type
Experimental
Arm Description
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;
Intervention Type
Drug
Intervention Name(s)
DMPS
Other Intervention Name(s)
Sodium Dimercaptosulphonate
Intervention Description
Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days;
Intervention Type
Drug
Intervention Name(s)
Penicillamine
Intervention Description
Dosage Form: Penicillamine: 250-1500mg per day, Frequency:TID,Duration: 5 years;
Intervention Type
Drug
Intervention Name(s)
DMSA
Other Intervention Name(s)
Dimercaptosuccinic Acid
Intervention Description
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;
Intervention Type
Drug
Intervention Name(s)
Zinc gluconate
Intervention Description
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;
Primary Outcome Measure Information:
Title
Serum ceruloplasmin
Description
Serum ceruloplasmin concentration will be analysed using a validated assay
Time Frame
Five years
Title
24-hour urine copper
Description
24-hour urinary copper excretion is to be measured
Time Frame
Five years
Title
serum copper
Description
serum copper will be analysed using a validated assay
Time Frame
Five years
Title
White blood cell
Description
The white blood cell will be evaluated using a validated assay
Time Frame
Five years
Title
Platelet count
Description
The platelet count will be evaluated using a validated assay
Time Frame
Five years
Title
urine protein level
Description
The urine protein level will be collected using a validated assay
Time Frame
Five years
Title
Alanine transaminase
Description
The concentration of alanine transaminase will be collected using a validated assay
Time Frame
Five years
Title
blood creatinine
Description
The concentration of blood creatinine will be tested using a validated assay
Time Frame
Five years
Title
international normalized ratio
Description
The international normalized ratio will be analyzed
Time Frame
Five years
Title
hepatic fibrosis markers test
Description
The concentrations of procollagen III, collage IV and hyaluronidase will be evaluated using a validated assay
Time Frame
Five years
Title
bone mineral density test
Description
The bone mineral density will be tested using the dual energy X ray absorptiometry
Time Frame
Five years
Title
Abdominal ultrasound
Description
The abdominal ultrasound will be collected
Time Frame
Five years
Title
Urinary ultrasound
Description
The urinary ultrasound will be analyzed in patients
Time Frame
Five years
Title
Cranial MRI scan
Description
The cranial MRI scan will be analyzed in patients
Time Frame
Five years
Title
Unified Wilson's disease rating scale
Description
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
Time Frame
Five years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhi-Ying Wu, MD&PhD
Phone
+86-571-87783569
Email
zhiyingwu@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Yi Dong, MD&PhD
Phone
+8618367129345
Email
dongyi720@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhi-Ying Wu, MD&PhD
Organizational Affiliation
Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
econd Affiliated Hospital,Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhi-Ying Wu, MD&PhD
Phone
+86-571-87783569
Email
zhiyingwu@zju.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

The Individual Therapy for Patients With Wilson's Disease

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