免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / The Individual Therapy for Patients With Wilson's Disease

The Individual Therapy for Patients With Wilson's Disease

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.

Condition or disease Intervention/treatment Phase
Wilson's Disease Drug: DMPS Drug: Penicillamine Drug: DMSA Drug: Zinc gluconate Early Phase 1

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: The Individual Therapy for Patients With Wilson's Disease
Actual Study Start Date : March 15, 2019
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024
Arms and Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Sodium Dimercaptosulphonate

Drug: Penicillamine
Dosage Form: Penicillamine: 250-1500mg per day, Frequency:TID,Duration: 5 years;

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 Name: Dimercaptosuccinic Acid
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;
Outcome Measures
Primary Outcome Measures :
  1. Serum ceruloplasmin [ Time Frame: Five years ]
    Serum ceruloplasmin concentration will be analysed using a validated assay

  2. 24-hour urine copper [ Time Frame: Five years ]
    24-hour urinary copper excretion is to be measured

  3. serum copper [ Time Frame: Five years ]
    serum copper will be analysed using a validated assay

  4. White blood cell [ Time Frame: Five years ]
    The white blood cell will be evaluated using a validated assay

  5. Platelet count [ Time Frame: Five years ]
    The platelet count will be evaluated using a validated assay

  6. urine protein level [ Time Frame: Five years ]
    The urine protein level will be collected using a validated assay

  7. Alanine transaminase [ Time Frame: Five years ]
    The concentration of alanine transaminase will be collected using a validated assay

  8. blood creatinine [ Time Frame: Five years ]
    The concentration of blood creatinine will be tested using a validated assay

  9. international normalized ratio [ Time Frame: Five years ]
    The international normalized ratio will be analyzed

  10. hepatic fibrosis markers test [ Time Frame: Five years ]
    The concentrations of procollagen III, collage IV and hyaluronidase will be evaluated using a validated assay

  11. bone mineral density test [ Time Frame: Five years ]
    The bone mineral density will be tested using the dual energy X ray absorptiometry

  12. Abdominal ultrasound [ Time Frame: Five years ]
    The abdominal ultrasound will be collected

  13. Urinary ultrasound [ Time Frame: Five years ]
    The urinary ultrasound will be analyzed in patients

  14. Cranial MRI scan [ Time Frame: Five years ]
    The cranial MRI scan will be analyzed in patients

  15. Unified Wilson's disease rating scale [ Time Frame: 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


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Zhi-Ying Wu, MD&PhD +86-571-87783569 zhiyingwu@zju.edu.cn
Contact: Yi Dong, MD&PhD +8618367129345 dongyi720@zju.edu.cn

Locations
Layout table for location information
China, Zhejiang
econd Affiliated Hospital,Zhejiang University School of Medicine Recruiting
Hangzhou, Zhejiang, China, 310009
Contact: Zhi-Ying Wu, MD&PhD    +86-571-87783569    zhiyingwu@zju.edu.cn   
Sponsors and Collaborators
Second Affiliated Hospital, School of Medicine, Zhejiang University
Investigators
Layout table for investigator information
Principal Investigator: Zhi-Ying Wu, MD&PhD Zhejiang University
Tracking Information
First Submitted Date  ICMJE April 8, 2019
First Posted Date  ICMJE May 21, 2019
Last Update Posted Date May 21, 2019
Actual Study Start Date  ICMJE March 15, 2019
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2019)
  • Serum ceruloplasmin [ Time Frame: Five years ]
    Serum ceruloplasmin concentration will be analysed using a validated assay
  • 24-hour urine copper [ Time Frame: Five years ]
    24-hour urinary copper excretion is to be measured
  • serum copper [ Time Frame: Five years ]
    serum copper will be analysed using a validated assay
  • White blood cell [ Time Frame: Five years ]
    The white blood cell will be evaluated using a validated assay
  • Platelet count [ Time Frame: Five years ]
    The platelet count will be evaluated using a validated assay
  • urine protein level [ Time Frame: Five years ]
    The urine protein level will be collected using a validated assay
  • Alanine transaminase [ Time Frame: Five years ]
    The concentration of alanine transaminase will be collected using a validated assay
  • blood creatinine [ Time Frame: Five years ]
    The concentration of blood creatinine will be tested using a validated assay
  • international normalized ratio [ Time Frame: Five years ]
    The international normalized ratio will be analyzed
  • hepatic fibrosis markers test [ Time Frame: Five years ]
    The concentrations of procollagen III, collage IV and hyaluronidase will be evaluated using a validated assay
  • bone mineral density test [ Time Frame: Five years ]
    The bone mineral density will be tested using the dual energy X ray absorptiometry
  • Abdominal ultrasound [ Time Frame: Five years ]
    The abdominal ultrasound will be collected
  • Urinary ultrasound [ Time Frame: Five years ]
    The urinary ultrasound will be analyzed in patients
  • Cranial MRI scan [ Time Frame: Five years ]
    The cranial MRI scan will be analyzed in patients
  • Unified Wilson's disease rating scale [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Individual Therapy for Patients With Wilson's Disease
Official Title  ICMJE The Individual Therapy for Patients With Wilson's Disease
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 Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Wilson's Disease
Intervention  ICMJE
  • Drug: DMPS
    Dosage Form: DMPS: 500-1000mg per day,DMPS Frequency:BID,DMPS Duration: 6 days;
    Other Name: Sodium Dimercaptosulphonate
  • Drug: Penicillamine
    Dosage Form: Penicillamine: 250-1500mg per day, Frequency:TID,Duration: 5 years;
  • 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 Name: Dimercaptosuccinic Acid
  • 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;
Study Arms  ICMJE
  • 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;
    Interventions:
    • Drug: DMPS
    • Drug: DMSA
  • 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;

    Interventions:
    • Drug: DMPS
    • Drug: DMSA
  • 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;

    Interventions:
    • Drug: DMPS
    • Drug: DMSA
  • 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;

    Interventions:
    • Drug: DMPS
    • Drug: DMSA
  • 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;
    Interventions:
    • Drug: DMPS
    • Drug: Penicillamine
    • Drug: DMSA
  • 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;

    Intervention: Drug: Zinc gluconate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 19, 2019) 		400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zhi-Ying Wu, MD&PhD +86-571-87783569 zhiyingwu@zju.edu.cn
Contact: Yi Dong, MD&PhD +8618367129345 dongyi720@zju.edu.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03957720
Other Study ID Numbers  ICMJE WuZYLab-WD
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Second Affiliated Hospital, School of Medicine, Zhejiang University
Study Sponsor  ICMJE Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Zhi-Ying Wu, MD&PhD Zhejiang University
PRS Account Second Affiliated Hospital, School of Medicine, Zhejiang University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯