Synergistic Enteral Regimen for Treatment of the Gangliosidoses
Keywords
Abstract
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).
Dates
| Last Verified: | 04/30/2019 |
| First Submitted: | 12/16/2013 |
| Estimated Enrollment Submitted: | 01/06/2014 |
| First Posted: | 01/07/2014 |
| Last Update Submitted: | 05/23/2019 |
| Last Update Posted: | 05/28/2019 |
| Actual Study Start Date: | 12/21/2015 |
| Estimated Primary Completion Date: | 08/30/2019 |
| Estimated Study Completion Date: | 08/30/2019 |
Condition or disease
Intervention/treatment
Drug: Syner-G Therapy Regimen
Other: Syner-G Therapy Regimen
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: 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. | Drug: Syner-G Therapy Regimen The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study. |
Eligibility Criteria
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: 1. Subjects must have a documented infantile or juvenile gangliosidosis disease. 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: 1. A desire to not participate 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. |
Outcome
Primary Outcome Measures
1. The duration of survival of each research subject, measured in months and years [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 Outcome Measures
1. Rate of Change in Neurocognitive Functioning [Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment]
