Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 4 for:    "Gangliosidosis" | "Anti-Retroviral Agents"

Effects of Miglustat Therapy on Infantile Type of Sandhoff and Taysachs Diseases (EMTISTD) (EMTISTD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03822013
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : January 30, 2019
Sponsor:
Collaborators:
Mashhad University of Medical Sciences
Kashan University of Medical Sciences
Information provided by (Responsible Party):
Tavasoli, Tehran University of Medical Sciences

Tracking Information
First Submitted Date  ICMJE January 22, 2019
First Posted Date  ICMJE January 30, 2019
Last Update Posted Date January 30, 2019
Actual Study Start Date  ICMJE January 14, 2019
Estimated Primary Completion Date January 14, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
  • Hospitalization frequency change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.
  • Pneumonia aspiration frequency change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.
  • Seizure Frequency change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.
  • Route of feeding change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.
  • motor function change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
quality of life change [ Time Frame: Baseline and 1year ]
A total score is reported according to Pediatric Quality Of Life Inventory Infant Scales. Total score range is between 0-45 and higher values represent worse outcomes.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
quality of life change: Infant/ Toddler Quality Of Life Questionnaire [ Time Frame: Baseline and 1year ]
Infant/ Toddler Quality Of Life Questionnaire
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Miglustat Therapy on Infantile Type of Sandhoff and Taysachs Diseases (EMTISTD)
Official Title  ICMJE Survey of Miglustat Therapeutic Effects on Neurological and Systemic Symptoms of Infantile Type of Sandhoff and Taysachs Diseases
Brief Summary

GM2 gangliosidosis is an autosomal recessive subtype of Lysosomal Storage Diseases in which, Hexosaminidase A-B deficiency is caused by HEXA-B gene. HEXA deficiency is seen in Tay sachs and HEXB deficiency causes Sandhoff disease.

Infantile forms of Sandhoff and Tay sachs are often lethal and management of the patients is supportive including nutrition, hydration, seizure control and management of respiratory problems. Recent studies have suggested new methods of treatment, such as enzyme replacement therapy, bone marrow transplantation and substrate reduction therapy.

The first drug used in SRT was Miglustat. It was introduced in 1980 as an anti HIV agent and later, it was registered under the trademark of Zavesca in 2009 and was used in treatment of Gaucher and Niemann-Pick disease. Zavesca passes blood brain barrier, so causes reduction of cholesterol and glycosphingolipids CNS neurons and relief of neurologic manifestations. Improvements were seen in oculomotor function, cognition, swallowing, motor disturbances and psychological problems after treatment with Zavesca. No effect has been proved on visceral involvement. Weight loss during first year of treatment, diarrhea and dyspepsia are seen as side effects.

Studies on SRT in lysosomal storage disease have different results. Some show improvements in manifestations of Gausche, Sandhoff & Tay sachs disease, while others show no valuable benefit for this method of treatment.

Finding an effective treatment for these chronic diseases can improve quality of life for the patients and their families, and also reduce costs for healthcare services. The controversy persists and more studies are needed for judgment. So this study is done to evaluate the effect of Miglustat therapy in Sandhoff and Tay sachs disease, and is believed to help for further studies in this field.

Detailed Description

This study is a before-after, open label clinical trial. Patients are all registered with diagnosis of Sandhoff and Tay sachs, and recruited at children's medical center Tehran-IRAN. Diagnosis is confirmed by enzyme level and genetic tests. Patients receive Miglustat therapy for 1 year and frequently assessed. After treatment cessation, patients will be followed up for 1 more year.

Treatment with Miglustat starts for one year. Patients are evaluated for neurologic examination, seizure, nasogastric tube insertion, aspiration pneumonia and quality of life at the beginning of treatment and every 3 months. Also randomized control trial is the gold standard for establishing efficacy in a research setting; there are ethical concerns about placebo control group in rare disease like Sandhoff and Tay sachs. Miglustat is considered as an Orphan drug so clinical trials about this drug are designed small and adjusted to limited population.

Variables in neurologic examination are Muscle tone, Muscular atrophy and contracture. motor function is scored according to "Gross Motor Function Classification System" (GMFCS) and quality of life is assessed by Infant Toddle Quality Of Life (ITQOL) questionnaire, with confirmed validity and stability.

Treatment started with Zavesca. Data gathered during frequent visits is registered in check lists and analyzed with SPSS version 18. Quantitative variables express with mean and standard deviation and qualitative variables with frequency and percentile. Analysis of variance for repeated measurements (ANOVA) and nonparametric freedman are tests using for comparisons of Outcomes. Sample size is calculated by formula for clinical trials with repeated measures.

Miglustat is FDA approved for Gaucher and Niemann pick diseases. All patients fill the informed consent and the nature of the study is explained to them. The information of participants is kept confidential. They are informed about side effects of the drug. If any cases at any time decides to exclude themselves from the study they are free to do so.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Although randomized control trial is the gold standard for clinical trial studies; there are ethical concerns about placebo control group in rare diseases such as Sandhoff and Tay sachs diseases.
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • GM2 Gangliosidosis
  • Supportive Care
Intervention  ICMJE Drug: Miglustat
Treatment with Zavesca regimen based on body surface area as follows: SQRT [Height (cm) × Weight (kg)] / 3600 <1.25 : 200mg TDS 0.88- 1.25: 200mg BID 0.73- 0.88: 100 mg TDS 0.47- 0.73: 100 mg BID <0.47: 100 mg Daily
Other Name: Zavesca
Study Arms  ICMJE Experimental: Miglustat
Intervention: Drug: Miglustat
Publications *

*   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: January 29, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 14, 2021
Estimated Primary Completion Date January 14, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Clinically and enzymatically suspected infants of Sandhoff (SD)/Tay-Sachs (TSD) diseases followed confirmation by molecular study.

Exclusion Criteria:

  • Renal impairment
  • Loss of follow up
  • Other systemic diseases
  • Concomitant drug therapy which may affect neurological system function
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 24 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alireza Tavasoli, MD 00989155130257 alirezatavasoli236@gmail.com
Contact: Sare Hoseinpour, MD 00989122103831 hosseipour.sare@gmail.com
Listed Location Countries  ICMJE Iran, Islamic Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03822013
Other Study ID Numbers  ICMJE 97-01-30-36953
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Tavasoli, Tehran University of Medical Sciences
Study Sponsor  ICMJE Tehran University of Medical Sciences
Collaborators  ICMJE
  • Mashhad University of Medical Sciences
  • Kashan University of Medical Sciences
Investigators  ICMJE Not Provided
PRS Account Tehran University of Medical Sciences
Verification Date January 2019

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