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Trial record 5 of 17 for:    Sandhoff Disease

Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G)

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ClinicalTrials.gov Identifier: NCT02030015
Recruitment Status : Recruiting
First Posted : January 8, 2014
Last Update Posted : October 26, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

December 17, 2013
January 8, 2014
October 26, 2017
March 2014
March 2019   (Final data collection date for 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 ]
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.
Rate of Change in Neurocognitive Functioning [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
The Bayley Scales of Infant and Toddler Development will be administered upon enrollment and annually thereafter for five years. The assessed neurocognitive functional domains shall include expressive communication, receptive communication, fine motor skills, and gross motor skills. The rate of change in the resulting data (i.e. slope) will be calculated over the duration of follow-up, and will compared to available natural history data. This measurement and analysis will be performed separately for each of the two gangliosidoses sub-types: infantile onset and juvenile onset.
Complete list of historical versions of study NCT02030015 on ClinicalTrials.gov Archive Site
Rate of Change in Neurocognitive Functioning [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
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.
  • Rate of Change in Adaptive Behavior [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    The Vineland Adaptive Behavior Scales will be administered upon enrollment and annually thereafter for five years. The assessed functional domain is the research subject's adaptive behavior. The rate of change in the resulting data (i.e. slope) will be calculated over the duration of follow-up, and will compared to available natural history data. This measurement and analysis will be performed separately for each of the two gangliosidoses sub-types: infantile onset and juvenile onset.
  • Quality-of-Life Measure Specific to the Infantile-Onset Gangliosidoses [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    The Living Infantile Tay-Sachs Questionnaire will be administered to the caregivers of research subjects who have infantile-onset Tay-Sachs disease. The domain being assessed is the research subject's quality of life.
  • Quality-of-Life Measure Specific to the Juvenile-Onset Gangliosidoses [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    The Living Juvenile Tay-Sachs Questionnaire will be administered to the caregivers of research subjects who have juvenile-onset Tay-Sachs disease; and if the subject has the ability to respond, to the research subject. The domain being assessed is the research subject's quality of life.
  • Biomarker Analysis and Identification in Research Subjects' Cerebrospinal Fluid and Serum [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    Research subjects' cerebrospinal fluid and serum will be collected upon enrollment and annually for five years. These procedures will be performed by a qualified physician while the research subject is under general anesthesia. These samples will be extensively analyzed to identify potential molecular biomarkers that may be associated with disease severity and/or changes in disease status. Such biomarkers may be useful for sensitively indicating disease progression and as outcomes measures for any future treatments.
  • Assessment of Change in Optic Nerve Atrophy and the Characteristic Retinal "Cherry Red Spot" [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    A qualified ophthalmologist will perform assessment of change in research subjects' optic nerve atrophy and their characteristic retinal "cherry red spot," upon enrollment and annually for five years. This assessment will be performed while the research subject is under general anesthesia.
  • Assessment of Changes in Research Subjects' Cardiac Health [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    A qualified cardiologist will perform assessment of research subjects' cardiac health, including cardiac output, ejection fraction, and cardiomyopathies. This assessment will be performed upon enrollment and annually for five years.
  • Assessment of Changes in Research Subjects' Seizure Frequency and Severity [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    Changes in research subjects' seizure frequency and severity will be assessed by a qualified neurologist, using interviews of the research subjects' caregivers. This assessment will be performed upon enrollment and annually for five years.
  • Assessment of Changes in Anatomical and Structural Characteristics of Research Subjects' Brains [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ]
    Changes in research subjects' total brain volume, intracranial brain volumes of interest, and specific brain structures will be assessed upon enrollment and annually for five years. The change-assessment tool shall be semi-automated quantitative measurements made from research subjects' magnetic resonance imaging (MRI) brain data. The MRI brain data shall be gathered while the research subjects are under general anesthesia.
  • The duration of survival of each research subject, measured in months [ 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 and the investigators' extensive clinical experience, in order to arrive at an expert assessment of the impact of the Syner-G therapy upon patient longevity.
Not Provided
Not Provided
 
Synergistic Enteral Regimen for Treatment of the Gangliosidoses
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.

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).

Interventional
Phase 4
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • GM1 Gangliosidoses
  • GM2 Gangliosidoses
  • Tay-Sachs Disease
  • Sandhoff Disease
  • Drug: miglustat
    The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study.
    Other Name: Zavesca®
  • Other: 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.
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.
Interventions:
  • Drug: miglustat
  • Other: Ketogenic Diet

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
6
March 2019
March 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
up to 204 Months   (Child)
No
Contact: Jeanine R. Jarnes, PharmD 612-626-5131 utzx0002@umn.edu
Contact: Evelyn S. Redtree, M.S. 612-625-0974 eredtree@umn.edu
United States
 
 
NCT02030015
Syner_G_Regimen
U54NS065768 ( U.S. NIH Grant/Contract )
1311M46101 ( Other Identifier: Univ. of Minnesota IRB Identifier Number )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
Plan Description: 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.
University of Minnesota - Clinical and Translational Science Institute
University of Minnesota - Clinical and Translational Science Institute
  • Rare Diseases Clinical Research Network
  • National Center for Advancing Translational Science (NCATS)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Lysosomal Disease Network
Principal Investigator: Jeanine R. Jarnes, PharmD University of Minnesota Fairview Hospital
University of Minnesota - Clinical and Translational Science Institute
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP