Clinical trial NCT02030015: Synergistic Enteral Regimen for Treatment of the Gangliosidoses
Official title: Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: GM1 Gangliosidoses
GM2 Gangliosidoses
Tay-Sachs Disease
Sandhoff Disease
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
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Rare Diseases Clinical Research Network
name: National Center for Advancing Translational Sciences (NCATS)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Lysosomal Disease Network
First posted: 2014-01-08
Enrollment: 16
Sex: ALL
Maximum age (years): 204
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 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).

Eligibility 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.

Primary outcomes:
measure: The Duration of Survival of Each Research Subject, Measured in Months and Years
timeFrame: 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:
measure: Rate of Change in Neurocognitive Functioning
timeFrame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota Fairview Hospital
name: Jeanine R. Jarnes, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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