A Phase 4 interventional study of miglustat and Ketogenic Diet in GM1 Gangliosidoses, GM2 Gangliosidoses and Tay-Sachs Disease, sponsored by University of Minnesota. Terminated at 1 site in United States. Open to participants aged Up to 204 Months. Per ClinicalTrials.gov, last updated 2021-04-14.
Sponsored by University of Minnesota · Phase 4, Interventional, and Treatment
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.
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).
26 studies on the registry are indexed under Gangliosidoses, GM2; 6 are open to participants now.
This study's enrollment of 16 is below the median of 21 across 14 interventional studies indexed under Gangliosidoses, GM2.
Browse Gangliosidoses, GM2 studies →University of Minnesota is the lead sponsor of 1,216 studies on the registry; 197 are open to participants now.
Of its 136 completed or terminated interventional studies of FDA-regulated products, 95 (70%) have results posted.
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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.
Drug: miglustat · Other: Ketogenic Diet
The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study.
Also known as: Zavesca®
The Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet for the 60-month duration of this study.
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.
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
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.
Time frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment
| Milestone | Syner-G Therapy Regimen |
|---|---|
| Started | 16 |
| Completed | 0 |
| Not completed | 16 |
| Withdrew: Withdrawal by subject | 3 |
| Withdrew: Death | 13 |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Collected over Participants were followed for the length of study participation; up to 60 months or 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Syner-G Therapy Regimen | 13/16 (81.3%) | 0/16 (0%) | 0/16 (0%) |
| Age, Categorical(Participants) | Syner-G Therapy Regimen |
|---|---|
| <=18 years | 16 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Syner-G Therapy Regimen |
|---|---|
| Female | 6 |
| Male | 10 |
| Race (NIH/OMB)(Participants) | Syner-G Therapy Regimen |
|---|---|
| American Indian or Alaska Native | 1 |
| Asian | 3 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 8 |
| More than one race | 2 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Syner-G Therapy Regimen |
|---|---|
| United States | 16 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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.
This study is terminated, as verified in Mar 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Miglustat