GM1 GangliosidosesPhase 4Syner-GNCT02030015
Synergistic Enteral Regimen for Treatment of the Gangliosidoses
A Phase 4 study testing miglustat and Ketogenic Diet in people with GM1 Gangliosidoses and GM2 Gangliosidoses, run by University of Minnesota at 1 site in United States.
Trial summary
The investigators hypothesize that a combination therapy using miglustat and the ketogenic diet for infantile and juvenile patients with gangliosidoses will create a synergy that 1) improves overall survival for patients with infantile or juvenile gangliosidoses, and 2) improves neurodevelopmental clinical outcomes of… Read more about this study
- Who is it for?
- Ages Up to 204 months
- Conditions the study is for
- GM1 Gangliosidoses, GM2 Gangliosidoses, Tay-Sachs Disease
- What is being tested?
- miglustat and Ketogenic Diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Dec 2015to 31 Jul 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 204 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Subjects must have a documented infantile or juvenile gangliosidosis disease.
- Age: 17 years or less at time of enrollment
- Subjects and their caregivers must be willing to work with a ketogenic diet team for management of the subject's ketogenic diet.
Who cannot join
- A desire to not participate
- Patients who are older than 17 years will not be enrolled in this study.
- Children with severe renal impairment will not be enrolled in this study.
- Post-pubertal females who are pregnant, or who are unwilling to use highly-effective methods to prevent pregnancy, will be excluded from this study.
- Breast-feeding females will be excluded from this study.
- Subjects who have an allergy to miglustat or any of the components within the drug product will be excluded from this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G)
The investigators hypothesize that a combination therapy using miglustat and the ketogenic diet for infantile and juvenile patients with gangliosidoses will create a synergy that 1) improves overall survival for patients with infantile or juvenile gangliosidoses, and 2) improves neurodevelopmental clinical outcomes of therapy, compared to data reported in previous natural history studies. The ketogenic diet is indicated for management of seizures in patients with seizure disorders. In this study, the ketogenic diet will be used to minimize or prevent gastrointestinal side-effects of miglustat. A Sandhoff disease mouse study has shown that the ketogenic diet may also improve central nervous system response to miglustat therapy (see Denny in "Citations" list below). Patients with infantile and juvenile gangliosidoses commonly suffer from seizure disorders, and use of the ketogenic diet in these patients may therefore also improve seizure management.
Read the detailed description
The infantile and juvenile forms of GM1 and GM2 gangliosidoses are neurodegenerative conditions that are lethal during childhood. There are no known effective therapies available for treatment of infantile and juvenile gangliosidoses. Studies of monotherapy with miglustat for treatment of these conditions have demonstrated safety, but have not demonstrated notable clinical improvement. To date, combination therapy for the infantile and juvenile gangliosidoses has not been explored. This study will evaluate a multi-targeted combination therapy for treatment of the gangliosidoses, using FDA approved therapies that have demonstrated safety in children. It is the aim of this study to learn if combination therapy using the "Syner-G" regimen (that is, synergistic enteral regimen for treatment of the gangliosidoses) will show improvement in overall survival and clinical benefits in neurodevelopmental abilities in children with gangliosidosis diseases.
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).
- Being tested
- miglustat, Ketogenic Diet
- Keywords
- infantile Tay-Sachs disease, juvenile Tay-Sachs disease, infantile GM1 gangliosidosis, juvenile GM1 gangliosidosis, infantile GM2 gangliosidosis, juvenile GM2 gangliosidosis, Sandhoff disease, gangliosidoses, miglustat, ketogenic diet, SYNER-G regimen, Syner-G, Zavesca, Tay-Sachs disease, Tay Sachs disease
- Medical subject headings
- Gangliosidoses, GM2, Tay-Sachs Disease, Sandhoff Disease, Tay-Sachs Disease, Juvenile, Gangliosidosis, GM1, Gangliosidoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
miglustatDrug
Also called Zavesca®
The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study.
Ketogenic DietOther
The Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet for the 60-month duration of this study.
| Study group | Role | What they receive |
|---|---|---|
| Syner-G Therapy Regimen | Experimental | 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. Receives: Drug: miglustat; Other: Ketogenic Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Duration of Survival of Each Research Subject, Measured in Months and Years
The survival duration of patients with infantile and juvenile forms of gangliosidoses will be assessed, in order to judge the clinical impact of the Syner-G therapy regimen. This will be accomplished by recording the subject's age on the date of enrollment in this study, and the subject's age at the conclusion of this study, or on the date of their death, whichever comes first. The duration of each subject's survival, expressed in months and years, will be compared to available natural history data in order to arrive at an expert assessment of the impact of the Syner-G therapy upon patient longevity.
Measured: From date of enrollment until 60 months thereafter, or the date of subject's death from any cause, whichever comes first, assessed up to 60 months
Secondary outcomes (1)
Rate of Change in Neurocognitive Functioning
The Bayley Scales of Infant and Toddler Development and the Vineland Adaptive Behavior Scales will be administered upon enrollment and annually thereafter for five years. Changes in these neurodevelopmental assessments will be evaluated over the duration of follow-up. Ability of the child to have these assessments yearly may be subject to patient's insurance coverage for such assessments.
Measured: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2014 (estimated)
- Study start22 Dec 2015
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Why it stopped: Efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for GM1 GangliosidosesStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Lysosomal Disease Network
- Responsible party
- Sponsor
- Investigators
- Jeanine R. Jarnes, PharmD, Principal investigator, University of Minnesota Fairview Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02030015
- Sponsor's protocol ID
- Syner_G_Regimen
- Other IDs
- U54NS065768, 1311M46101
- Acronym
- Syner-G
- Status last verified
- Mar 2021
- First submitted
- 17 Dec 2013
- Last updated
- 14 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management \& Coordinating Center ("DMCC"). Eventually this data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.
Publications
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.
PubMed 22025593Nalini A, Christopher R. Cerebral glycolipidoses: clinical characteristics of 41 pediatric patients. J Child Neurol. 2004 Jun;19(6):447-52. doi: 10.1177/088307380401900610.
PubMed 15446395Maegawa 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.
PubMed 17015493Maegawa 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.
PubMed 19447653Shapiro 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.
PubMed 19346952Belmatoug 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.
PubMed 21779792Kossoff 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.
PubMed 18823325Zaroff 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.
PubMed 15210895Bembi 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.
PubMed 16434676Zupec-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.
PubMed 19033218Denny 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.
PubMed 20374428Utz 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.
PubMed 25557439Karimzadeh 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.
PubMed 28716012Deodato 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.
PubMed 28577204Brackmann 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.
PubMed 28192816
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G)
- ClinicalTrials.gov ID
- NCT02030015
- Acronym / sponsor ID
- Syner-G / Syner_G_Regimen
- Keywords
- infantile Tay-Sachs disease, juvenile Tay-Sachs disease, infantile GM1 gangliosidosis, juvenile GM1 gangliosidosis, infantile GM2 gangliosidosis, juvenile GM2 gangliosidosis, Sandhoff disease, gangliosidoses
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Efficacy
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Lysosomal Disease Network
- Study start
- 22 Dec 2015 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 8 Jan 2014 (estimated)
- Results
- Posted 14 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that a combination therapy using miglustat and the ketogenic diet for infantile and juvenile patients with gangliosidoses will create a synergy that 1) improves overall survival for patients with infantile or juvenile gangliosidoses, and 2) improves neurodevelopmental clinical outcomes of therapy, compared to data reported in previous natural history studies. The ketogenic diet is indicated for management of seizures in patients with seizure disorders. In this study, the ketogenic diet will be used to minimize or prevent gastrointestinal side-effects of miglustat. A Sandhoff disease mouse study has shown that the ketogenic diet may also improve central nervous system response to miglustat therapy (see Denny in "Citations" list below). Patients with infantile and juvenile gangliosidoses commonly suffer from seizure disorders, and use of the ketogenic diet in these patients may therefore also improve seizure management.
Detailed description
The infantile and juvenile forms of GM1 and GM2 gangliosidoses are neurodegenerative conditions that are lethal during childhood. There are no known effective therapies available for treatment of infantile and juvenile gangliosidoses. Studies of monotherapy with miglustat for treatment of these conditions have demonstrated safety, but have not demonstrated notable clinical improvement. To date, combination therapy for the infantile and juvenile gangliosidoses has not been explored. This study will evaluate a multi-targeted combination therapy for treatment of the gangliosidoses, using FDA approved therapies that have demonstrated safety in children. It is the aim of this study to learn if combination therapy using the "Syner-G" regimen (that is, synergistic enteral regimen for treatment of the gangliosidoses) will show improvement in overall survival and clinical benefits in neurodevelopmental abilities in children with gangliosidosis diseases.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Syner-G Therapy Regimen | Experimental | Drug: miglustat, Other: Ketogenic DietThe 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. |
Who may qualify
- Ages
- Up to 204 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Subjects must have a documented infantile or juvenile gangliosidosis disease.
- Age: 17 years or less at time of enrollment
- Subjects and their caregivers must be willing to work with a ketogenic diet team for management of the subject's ketogenic diet.
Key exclusion criteria (6 listed)
- A desire to not participate
- Patients who are older than 17 years will not be enrolled in this study.
- Children with severe renal impairment will not be enrolled in this study.
- Post-pubertal females who are pregnant, or who are unwilling to use highly-effective methods to prevent pregnancy, will be excluded from this study.
- Breast-feeding females will be excluded from this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| miglustatAlso: Zavesca®The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study. | Drug | Syner-G Therapy Regimen |
| Ketogenic DietThe Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet for the 60-month duration of this study. | Other | Syner-G Therapy Regimen |
Primary outcome
The Duration of Survival of Each Research Subject, Measured in Months and Years
Time frame: From date of enrollment until 60 months thereafter, or the date of subject's death from any cause, whichever comes first, assessed up to 60 months
The survival duration of patients with infantile and juvenile forms of gangliosidoses will be assessed, in order to judge the clinical impact of the Syner-G therapy regimen. This will be accomplished by recording the subject's age on the date of enrollment in this study, and the subject's age at the conclusion of this study, or on the date of their death, whichever comes first. The duration of each subject's survival, expressed in months and years, will be compared to available natural history data in order to arrive at an expert assessment of the impact of the Syner-G therapy upon patient longevity.
1 secondary outcome
Rate of Change in Neurocognitive Functioning
Time frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22025593Bley 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.
- Background: PubMed 15446395Nalini A, Christopher R. Cerebral glycolipidoses: clinical characteristics of 41 pediatric patients. J Child Neurol. 2004 Jun;19(6):447-52. doi: 10.1177/088307380401900610.
- Background: PubMed 17015493Maegawa 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.
- Background: PubMed 19447653Maegawa 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.
- Background: PubMed 19346952Shapiro 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.
- Background: PubMed 21779792Belmatoug 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.
- Background: PubMed 18823325Kossoff 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.
- Background: PubMed 15210895Zaroff 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.
- Background: PubMed 16434676Bembi 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.
- Background: PubMed 19033218Zupec-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.
- Background: PubMed 20374428Denny 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.
- Background: PubMed 25557439Utz 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.
- Orphanet links to detailed information about the gangliosidosesLink provided by the sponsor.
- Educational information for the layperson about Tay-Sachs disease from the National Organization for Rare Disorders (NORD)Link provided by the sponsor.
- Educational information for the layperson about Tay-Sachs disease from the National Human Genome Research Institute at the NIHLink provided by the sponsor.
- 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.Link provided by the sponsor.
- Rare Diseases Clinical Research Network, an NIH-funded research networkLink provided by the sponsor.
- The Lysosomal Disease Network's page on the Rare Diseases Clinical Research Network's web siteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management \& Coordinating Center ("DMCC"). Eventually this data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeanine R. Jarnes, PharmD principal investigator
University of Minnesota Fairview Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing miglustat and Ketogenic Diet in people with GM1 Gangliosidoses and GM2 Gangliosidoses, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Duration of Survival of Each Research Subject, Measured in Months and Years (time frame: From date of enrollment until 60 months thereafter, or the date of subject's death from any cause, whichever comes first, assessed up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02030015, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2021.