Treatment Development for Glucose Transporter Type I Deficiency Syndrome (G1D)

Study Overview
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Brief Summary
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The purpose of this trial is to determine if an alternative energy source will impact brain metabolism in a disorder characterized by glucose metabolism failure in the brain. The central hypothesis tested in this investigation is whether circumventing impaired glucose metabolism is feasible, safe and potentially promising by supplying anaplerotic precursors through metabolism of odd-carbon fatty acids that can enter the citric acid cycle (CAC) through alternative metabolic pathways.

Detailed Description
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Triheptanoin, a nutritional supplement long used in other metabolic disorders and also added to foods and cosmetics, will be used to complement any diet that G1D patients may be receiving at enrollment with the exception of the ketogenic diet.

Official Title
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Clinical Trial of Citric Acid Cycle Stimulation in Energy-deficiency States: Treatment Development for Glucose Transporter Type I Deficiency Syndrome (G1D) (NMTUT 2010B)

Conditions
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Glucose Transporter Type 1 Deficiency Syndrome, GLUT1 Deficiency Syndrome

Intervention / Treatment
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* Drug: Triheptanoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female Ages 1 month to <21 years of age Diagnosed with glucose transporter type I deficiency. Age matched (within 1 year) controls not diagnosed with G1D. Exclusion Criteria: All subjects carrying body metal implants incompatible with the exposure to a magnetic field Subjects unable to tolerate the MRI and MRS procedures due to anxiety Subjects receiving oxygen supplementation or those confined to a bed or stretcher Subjects currently receiving a ketogenic diet, due to a high risk of seizure recurrence while transitioning off ketosis. Patients behaviorally unable to hold still for imaging procedures (rather than limited by seizure activity) will be excluded.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triheptanoin<br>Triheptanoin (C7 oil, liquid) dosed at 1 g/kg body weight divided and administered 4 times per day via mouth or g-tube for 3 months. | Drug: Triheptanoin<br>* Triheptanoin is a 7-carbon medium chain triglyceride<br>* Other names: Heptanoate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Reduction in Spike-wave Fraction of the EEG Recording Time | Visual analysis of EEG recording to determine the fraction of spike-range within the area of recording. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Change in Brain Metabolic Rate After 3 Months | Magnetic Resonance Imaging (MRI) used to calculate brain metabolic rate. Brain metabolic rate compared before oil ingestion (Baseline), 90 minutes after oil ingestion, and after 3 months of daily oil ingestion in each participant. Triheptanoin metabolism may lead to increased oxygen consumption only while the brain undergoes a reduction of ictogenesis. We hypothesize that when ictogenesis is abolished by triheptanoin or absent at baseline, triheptanoin exerts little or no effect on CMR02. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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G1D, Glut1 Disorder, Glucose Transporter Type 1 Disorder, Glucose Transporter Type I Disorder