Glucose Transporter Type 1 Deficiency Syndrome, GLUT1 Deficiency Syndrome
Conditions
Keywords
G1D, Glut1 Disorder, Glucose Transporter Type 1 Disorder, Glucose Transporter Type I Disorder
Brief summary
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
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.
Interventions
DRUGTriheptanoin
Triheptanoin is a 7-carbon medium chain triglyceride
Sponsors
Juan Pascual
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 20 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction in Spike-wave Fraction of the EEG Recording Time | 1 day | Visual analysis of EEG recording to determine the fraction of spike-range within the area of recording. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change in Brain Metabolic Rate After 3 Months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Triheptanoin 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. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Experimental: Triheptanoin |
|---|---|
| Age, Categorical <=18 years | 11 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 12.5 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 4 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
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.
Time frame: 1 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Triheptanoin | Number of Participants With Reduction in Spike-wave Fraction of the EEG Recording Time | 13 Participants |
Secondary
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.
Time frame: 3 months
Population: 5 participants out of the 14 total participants enrolled completed the optional MRI . Reasons for participants electing to not participate in imaging included inability to remain immobile due to movement disorder or anxiety, immaturity, metal implants, and personal choice.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Triheptanoin | Number of Participants With Change in Brain Metabolic Rate After 3 Months | 5 Participants |