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
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|
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 :||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|
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
- 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.
- 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.
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
|Contact: Alireza Tavasoli, MDfirstname.lastname@example.org|
|Contact: Sare Hoseinpour, MDemail@example.com|
|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 firstname.lastname@example.org|
|Tehran University Of Medical Sciences||Recruiting|
|Tehran, Iran, Islamic Republic of|
|Contact: Alireza Tavasoli, MD 00989155130257 email@example.com|
|Contact: Sare Hoseinpour, MD 00989122103831 firstname.lastname@example.org|
|Sub-Investigator: Mahmoud Reza Ashrafi, MD|
|Sub-Investigator: Motahare Talebian, MD|