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

NCT03822013 | Terminated Phase 3 DMC

• 1 other identifier: 97-01-30-36953
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

GM2 Gangliosidosis; Supportive Care

Keywords

Sandhoff Disease; Tay-Sachs Disease; Miglustat

Outcome Measures

Primary Outcomes (5)

• Hospitalization frequency change

  Method of measurement is checklist.

  Baseline and 4, 8, 12 months after intervention and 1-year without intervention

• Pneumonia aspiration frequency change

  Method of measurement is checklist.

  Baseline and 4, 8, 12 months after intervention and 1-year without intervention

• Seizure Frequency change

  Method of measurement is checklist.

  Baseline and 4, 8, 12 months after intervention and 1-year without intervention

• Route of feeding change

  Method of measurement is checklist.

  Baseline and 4, 8, 12 months after intervention and 1-year without intervention

• motor function change

  Method of measurement is checklist.

  Baseline and 4, 8, 12 months after intervention and 1-year without intervention

Secondary Outcomes (1)

• quality of life change

  Baseline and 1year

Study Arms (2)

Miglustat

EXPERIMENTAL

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

No Miglustat

NO INTERVENTION

Interventions

Miglustat DRUG

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

Also known as: Zavesca

Miglustat

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Renal impairment
• Loss of follow up
• Other systemic diseases
• Concomitant drug therapy which may affect neurological system function

Sponsors & Collaborators

• Tehran University of Medical Sciences: lead
• Mashhad University of Medical Sciences: collaborator
• Kashan University of Medical Sciences: collaborator

Study Sites (3)

Kashan University Of Medical Sciences

Kashan, Isfahan, Iran

Location

Mashhad University Of Medical Sciences

Mashhad, Khorasan, Iran

Location

Tehran University Of Medical Sciences

Tehran, Tehran Province, Iran

Location

Related Publications (9)

• Jarnes Utz JR, Kim S, King K, Ziegler R, Schema L, Redtree ES, Whitley CB. Infantile gangliosidoses: Mapping a timeline of clinical changes. Mol Genet Metab. 2017 Jun;121(2):170-179. doi: 10.1016/j.ymgme.2017.04.011. Epub 2017 Apr 29.

  PMID: 28476546 BACKGROUND

• Villamizar-Schiller IT, Pabon LA, Hufnagel SB, Serrano NC, Karl G, Jefferies JL, Hopkin RJ, Prada CE. Neurological and cardiac responses after treatment with miglustat and a ketogenic diet in a patient with Sandhoff disease. Eur J Med Genet. 2015 Mar;58(3):180-3. doi: 10.1016/j.ejmg.2014.12.009. Epub 2014 Dec 12.

  PMID: 25497207 BACKGROUND

• Masciullo M, Santoro M, Modoni A, Ricci E, Guitton J, Tonali P, Silvestri G. Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up. J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S355-61. doi: 10.1007/s10545-010-9186-3. Epub 2010 Sep 4.

  PMID: 20821051 BACKGROUND

• Shapiro BE, Pastores GM, Gianutsos J, Luzy C, Kolodny EH. Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment. Genet Med. 2009 Jun;11(6):425-33. doi: 10.1097/GIM.0b013e3181a1b5c5.

  PMID: 19346952 BACKGROUND

• Wortmann SB, Lefeber DJ, Dekomien G, Willemsen MA, Wevers RA, Morava E. Substrate deprivation therapy in juvenile Sandhoff disease. J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S307-11. doi: 10.1007/s10545-009-1261-2. Epub 2009 Nov 4.

  PMID: 19898952 BACKGROUND

• Tallaksen CM, Berg JE. Miglustat therapy in juvenile Sandhoff disease. J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S289-93. doi: 10.1007/s10545-009-1224-7. Epub 2009 Nov 4.

  PMID: 19898953 BACKGROUND

• Bembi B, Marchetti F, Guerci VI, Ciana G, Addobbati R, Grasso D, Barone R, Cariati R, Fernandez-Guillen L, Butters T, Pittis MG. Substrate reduction therapy in the infantile form of Tay-Sachs disease. Neurology. 2006 Jan 24;66(2):278-80. doi: 10.1212/01.wnl.0000194225.78917.de.

  PMID: 16434676 BACKGROUND

• Jacobs JF, Willemsen MA, Groot-Loonen JJ, Wevers RA, Hoogerbrugge PM. Allogeneic BMT followed by substrate reduction therapy in a child with subacute Tay-Sachs disease. Bone Marrow Transplant. 2005 Nov;36(10):925-6. doi: 10.1038/sj.bmt.1705155. No abstract available.

  PMID: 16151419 BACKGROUND

• Jeyakumar M, Norflus F, Tifft CJ, Cortina-Borja M, Butters TD, Proia RL, Perry VH, Dwek RA, Platt FM. Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation. Blood. 2001 Jan 1;97(1):327-9. doi: 10.1182/blood.v97.1.327.

  PMID: 11133779 BACKGROUND

MeSH Terms

Conditions

Gangliosidoses, GM2; Sandhoff Disease; Tay-Sachs Disease

Interventions

miglustat

Condition Hierarchy (Ancestors)

Gangliosidoses; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: 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.

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: January 30, 2019
• Study Start: January 14, 2019
• Primary Completion: September 10, 2025
• Study Completion: September 10, 2025
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

IR (3)