Synergistic Enteral Regimen for Treatment of the Gangliosidoses
NCT ID: NCT02030015
Last Updated: 2021-04-14
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE4
16 participants
INTERVENTIONAL
2015-12-22
2019-07-31
Brief Summary
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Detailed Description
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This study is planned as a 5-year longitudinal treatment study. Subjects will be started on the treatment regimen when they are enrolled in the study. Data will be collected during yearly evaluations and at completion of study. Investigators may choose to stop therapy at any time, as clinically indicated for individual patients.
The Ketogenic Diet is a special diet that contains higher amounts of fat and lower amounts of carbohydrate compared to an average diet. The purpose of this is to help reduce food-miglustat interactions. The ketogenic diet may also help in management of seizures in these patients. (The ketogenic diet has been used as an anti-seizure treatment in a variety of medical conditions for many decades.) A study in Sandhoff disease mice has shown that the ketogenic diet may also help miglustat be more effective in the central nervous system (see Denny in "Citations" list below).
Miglustat will be used to reduce the amount of ganglioside accumulation in the child's cells. Miglustat is not FDA approved for treatment of the gangliosidoses. It is FDA approved for a different inherited metabolic disease called Gaucher disease type I.
This study has been issued Investigational New Drug (IND) # 127636 by the U.S. Food and Drug Administration (FDA).
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Syner-G Therapy Regimen
The Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet, and daily treatment with orally-administered miglustat, for the duration of the 60-month study.
miglustat
The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study.
Ketogenic Diet
The Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet for the 60-month duration of this study.
Interventions
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miglustat
The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study.
Ketogenic Diet
The Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet for the 60-month duration of this study.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Age: 17 years or less at time of enrollment
3. Subjects and their caregivers must be willing to work with a ketogenic diet team for management of the subject's ketogenic diet.
Exclusion Criteria
2. Patients who are older than 17 years will not be enrolled in this study.
3. Children with severe renal impairment will not be enrolled in this study.
4. Post-pubertal females who are pregnant, or who are unwilling to use highly-effective methods to prevent pregnancy, will be excluded from this study.
5. Breast-feeding females will be excluded from this study.
6. Subjects who have an allergy to miglustat or any of the components within the drug product will be excluded from this study.
204 Months
ALL
No
Sponsors
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Rare Diseases Clinical Research Network
NETWORK
National Center for Advancing Translational Sciences (NCATS)
NIH
National Institute of Neurological Disorders and Stroke (NINDS)
NIH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
Lysosomal Disease Network
OTHER
University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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Jeanine R. Jarnes, PharmD
Role: PRINCIPAL_INVESTIGATOR
University of Minnesota Fairview Hospital
Locations
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University of Minnesota
Minneapolis, Minnesota, United States
Countries
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References
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Bley AE, Giannikopoulos OA, Hayden D, Kubilus K, Tifft CJ, Eichler FS. Natural history of infantile G(M2) gangliosidosis. Pediatrics. 2011 Nov;128(5):e1233-41. doi: 10.1542/peds.2011-0078. Epub 2011 Oct 24.
Nalini A, Christopher R. Cerebral glycolipidoses: clinical characteristics of 41 pediatric patients. J Child Neurol. 2004 Jun;19(6):447-52. doi: 10.1177/088307380401900610.
Maegawa GH, Stockley T, Tropak M, Banwell B, Blaser S, Kok F, Giugliani R, Mahuran D, Clarke JT. The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported. Pediatrics. 2006 Nov;118(5):e1550-62. doi: 10.1542/peds.2006-0588. Epub 2006 Oct 2.
Maegawa GH, van Giersbergen PL, Yang S, Banwell B, Morgan CP, Dingemanse J, Tifft CJ, Clarke JT. Pharmacokinetics, safety and tolerability of miglustat in the treatment of pediatric patients with GM2 gangliosidosis. Mol Genet Metab. 2009 Aug;97(4):284-91. doi: 10.1016/j.ymgme.2009.04.013. Epub 2009 May 3.
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.
Belmatoug N, Burlina A, Giraldo P, Hendriksz CJ, Kuter DJ, Mengel E, Pastores GM. Gastrointestinal disturbances and their management in miglustat-treated patients. J Inherit Metab Dis. 2011 Oct;34(5):991-1001. doi: 10.1007/s10545-011-9368-7. Epub 2011 Jul 21.
Kossoff EH, Zupec-Kania BA, Amark PE, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Helen Cross J, Dahlin MG, Donner EJ, Klepper J, Jehle RS, Kim HD, Christiana Liu YM, Nation J, Nordli DR Jr, Pfeifer HH, Rho JM, Stafstrom CE, Thiele EA, Turner Z, Wirrell EC, Wheless JW, Veggiotti P, Vining EP; Charlie Foundation, Practice Committee of the Child Neurology Society; Practice Committee of the Child Neurology Society; International Ketogenic Diet Study Group. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia. 2009 Feb;50(2):304-17. doi: 10.1111/j.1528-1167.2008.01765.x. Epub 2008 Sep 23.
Zaroff CM, Neudorfer O, Morrison C, Pastores GM, Rubin H, Kolodny EH. Neuropsychological assessment of patients with late onset GM2 gangliosidosis. Neurology. 2004 Jun 22;62(12):2283-6. doi: 10.1212/01.wnl.0000130498.19019.02.
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.
Zupec-Kania BA, Spellman E. An overview of the ketogenic diet for pediatric epilepsy. Nutr Clin Pract. 2008 Dec-2009 Jan;23(6):589-96. doi: 10.1177/0884533608326138.
Denny CA, Heinecke KA, Kim YP, Baek RC, Loh KS, Butters TD, Bronson RT, Platt FM, Seyfried TN. Restricted ketogenic diet enhances the therapeutic action of N-butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice. J Neurochem. 2010 Jun;113(6):1525-35. doi: 10.1111/j.1471-4159.2010.06733.x. Epub 2010 Apr 3.
Utz JR, Crutcher T, Schneider J, Sorgen P, Whitley CB. Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses. Mol Genet Metab. 2015 Feb;114(2):274-80. doi: 10.1016/j.ymgme.2014.11.015. Epub 2014 Dec 6.
Karimzadeh P, Naderi S, Modarresi F, Dastsooz H, Nemati H, Farokhashtiani T, Shamsian BS, Inaloo S, Faghihi MA. Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene. BMC Med Genet. 2017 Jul 17;18(1):73. doi: 10.1186/s12881-017-0417-4.
Deodato F, Procopio E, Rampazzo A, Taurisano R, Donati MA, Dionisi-Vici C, Caciotti A, Morrone A, Scarpa M. The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression. Metab Brain Dis. 2017 Oct;32(5):1529-1536. doi: 10.1007/s11011-017-0044-y. Epub 2017 Jun 3.
Brackmann F, Kehrer C, Kustermann W, Bohringer J, Krageloh-Mann I, Trollmann R. Rare Variant of GM2 Gangliosidosis through Activator-Protein Deficiency. Neuropediatrics. 2017 Apr;48(2):127-130. doi: 10.1055/s-0037-1598646. Epub 2017 Feb 13.
Regier DS, Proia RL, D'Azzo A, Tifft CJ. The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy. Pediatr Endocrinol Rev. 2016 Jun;13 Suppl 1(Suppl 1):663-73.
Nestrasil I, Ahmed A, Utz JM, Rudser K, Whitley CB, Jarnes-Utz JR. Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study. Mol Genet Metab. 2018 Feb;123(2):97-104. doi: 10.1016/j.ymgme.2017.12.432. Epub 2017 Dec 20.
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.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
Access external resources that provide additional context or updates about the study.
Educational information for the layperson about Tay-Sachs disease from the National Organization for Rare Disorders (NORD)
Educational information for the layperson about Tay-Sachs disease from the National Human Genome Research Institute at the NIH
Talking Glossary of Genetic Terms from the National Human Genome Research Institute at the NIH. (Uses Adobe Flash plugin.) This Talking Glossary is also available as an app for mobile devices, from a link on this page.
Rare Diseases Clinical Research Network, an NIH-funded research network
The Lysosomal Disease Network's page on the Rare Diseases Clinical Research Network's web site
Other Identifiers
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1311M46101
Identifier Type: OTHER
Identifier Source: secondary_id
Syner_G_Regimen
Identifier Type: -
Identifier Source: org_study_id
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