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

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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

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.


Condition or disease Intervention/treatment Phase
GM2 Gangliosidosis Supportive Care Drug: Miglustat Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
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
Official Title: Survey of Miglustat Therapeutic Effects on Neurological and Systemic Symptoms of Infantile Type of Sandhoff and Taysachs Diseases
Actual Study Start Date : January 14, 2019
Estimated Primary Completion Date : January 14, 2020
Estimated Study Completion Date : January 14, 2021


Arm Intervention/treatment
Experimental: Miglustat 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




Primary Outcome Measures :
  1. Hospitalization frequency change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.

  2. Pneumonia aspiration frequency change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.

  3. Seizure Frequency change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.

  4. Route of feeding change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.

  5. motor function change [ Time Frame: Baseline and 4, 8, 12 months after intervention and 1-year without intervention ]
    Method of measurement is checklist.


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   6 Months to 24 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03822013


Contacts
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Contact: Alireza Tavasoli, MD 00989155130257 alirezatavasoli236@gmail.com
Contact: Sare Hoseinpour, MD 00989122103831 hosseipour.sare@gmail.com

Locations
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Iran, Islamic Republic of
Kashan University Of Medical Sciences Recruiting
Kashan, Isfahan, Iran, Islamic Republic of
Contact: Ahmad Talebian, MD    00989131629456    Talebianmd@yahoo.com   
Mashhad University Of Medical Sciences Recruiting
Mashhad, Khorasan, Iran, Islamic Republic of
Contact: Mehran Beiraghi, MD    00989155080287    beiraghitm1@gmail.com   
Tehran University Of Medical Sciences Recruiting
Tehran, Iran, Islamic Republic of
Contact: Alireza Tavasoli, MD    00989155130257    a_tavasoli@sina.tums.ac.ir   
Contact: Sare Hoseinpour, MD    00989122103831    hosseinpour.sare@gmail.com   
Sub-Investigator: Mahmoud Reza Ashrafi, MD         
Sub-Investigator: Motahare Talebian, MD         
Sponsors and Collaborators
Tehran University of Medical Sciences
Mashhad University of Medical Sciences
Kashan University of Medical Sciences

Publications:

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Responsible Party: Tavasoli, Principal investigator, Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT03822013     History of Changes
Other Study ID Numbers: 97-01-30-36953
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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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

Keywords provided by Tavasoli, Tehran University of Medical Sciences:
Sandhoff Disease
Tay-Sachs Disease
Miglustat

Additional relevant MeSH terms:
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Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Gangliosidoses
Gangliosidoses, GM2
Tay-Sachs Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lipidoses
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Miglustat
1-Deoxynojirimycin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs