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

April 15, 2024 updated by: Tavasoli, Tehran University of Medical Sciences

Survey of Miglustat Therapeutic Effects on Neurological and Systemic Symptoms of Infantile Type of Sandhoff and Taysachs Diseases

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a case- control, 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. Case group receive Miglustat therapy for 1 year and frequently assessed. Patients in control group are also assessed for 1 year without receiving Miglustat.

Patients are evaluated for neurologic examination, seizure, nasogastric tube insertion, aspiration pneumonia and quality of life at the beginning of study and every 3 months. 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.

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

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Iran, Islamic Republic of
      • Tehran, Iran, Islamic Republic of
        • Recruiting
        • Tehran University Of Medical Sciences
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Mahmoud Reza Ashrafi, MD
        • Sub-Investigator:
          • Motahare Talebian, MD
    • Isfahan
      • Kashan, Isfahan, Iran, Islamic Republic of
        • Recruiting
        • Kashan University Of Medical Sciences
        • Contact:
    • Khorasan
      • Mashhad, Khorasan, Iran, Islamic Republic of
        • Recruiting
        • Mashhad University Of Medical Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 2 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Miglustat

Miglustat is administered, dose is adjusted according to Body Surface Area as below:

>1.25 : 200 mg TDS 0.88-1.25 : 200mg BID 0.73-0.88 :100mg TDS 0.47-0.73 : 100mg BID <0.47 :100mg daily
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 Names:
  • Zavesca
No Intervention: No Miglustat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospitalization frequency change
Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Method of measurement is checklist.
Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Pneumonia aspiration frequency change
Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Method of measurement is checklist.
Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Seizure Frequency change
Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Method of measurement is checklist.
Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Route of feeding change
Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Method of measurement is checklist.
Baseline and 4, 8, 12 months after intervention and 1-year without intervention
motor function change
Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention
Method of measurement is checklist.
Baseline and 4, 8, 12 months after intervention and 1-year without intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and 1year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tehran University of Medical Sciences

Collaborators

Mashhad University of Medical Sciences
Kashan University of Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 14, 2019

Primary Completion (Estimated)

December 15, 2024

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

January 22, 2019

First Submitted That Met QC Criteria

January 29, 2019

First Posted (Actual)

January 30, 2019

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 97-01-30-36953

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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