GLUT1DS1
Conditions
Keywords
G1D, glucose, transporter
Brief summary
To explore triheptanoin (C7 oil) compatibility with the ketogenic diet by evaluating EEG, and seizure rate, glycemia and ketosis in proven G1D patients receiving a ketogenic diet.
Detailed description
This is a single site, open label proof of principle exploratory trial to investigate the compatibility of C7 oil with the ketogenic diet in subjects diagnosed with G1D. The ketogenic diet will have been previously described by the patient's treating physician independently of this study and for clinical reasons. The ketogenic diet supplies over 50% of calories from fat, subjects, who are already tolerating over this much fat as part of their previously prescribed ketogenic diet, will replace 45% of their daily caloric intake with the triheptanoin for 24 hours, during a 48 hour inpatient stay. Subjects will have a continuous EEG to monitor for any potential C7 related changes in seizure before, during, and after triheptanoin oil ingestion.
Interventions
DRUGTriheptanoin
Dietary supplementation with triheptanoin
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Months to 35 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of glucose transporter type 1 deficiency (G1D), confirmed by clinical genotyping at a CLIA-certified laboratory. * Stable on ketogenic diet at 2.5:1 to 4:1 ratio (i.e., no changes in ratio will have taken place for 2 months). The initiation of a ketogenic diet is previous to - and thus is not part of this study. * Males and females 30 months to 35 years and 11 months old inclusive.
Exclusion criteria
* Subjects with evidence of independent, unrelated metabolic and/or genetic disease. * Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, crohn's disease, or colitis that could increase the subject's risk of developing diarrhea or stomach pain. * Subjects with a BMI (body mass index) greater than or equal to 30. * Subjects currently not on ketogenic diet. * Women who are pregnant or breast feeding may not participate. Women who plan to become pregnant during the course of the study, or who are unwilling to use birth control to prevent pregnancy (including abstinence) may not participate. Females age 10 and over will be asked to provide a urine sample for a pregnancy test via dipstick. Subjects will be asked to agree to abstinence or another form of birth control for the duration of the study. * Allergy/sensitivity to C7 * Previous use of triheptanoin less than 1 month prior to study initiation. * Treatment with medium chain triglycerides in the last 24 hours. * Subjects exhibiting signs of dementia, or diagnosed with any degenerative brain disorder (such as Alzheimer's disease) that would confound assessment of cognitive changes, in the opinion of the investigator. * Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements. * Inability or unwillingness of subject or legal guardian/representative to give written informed consent, or assent for children age 10-17, * Addition of a new antiseizure drug in the previous 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ketosis (Beta-hydroxybutyrate Levels) | Day 1, Day 4 | Change in Ketosis as measured by changes in blood beta-hydroxybutyric acid levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fraction of Subjects (of a Total of 10 Studied) Who Exhibit a Change in Observable Seizure Rate | Baseline (Day 1) - Day 4 | The percent change in observable seizure rate is measured as the change in observable seizure numbers from baseline to Day 4. Seizure rate is defined as count of seizures per patient per day. |
| Change in Glycemia | Day 1 - Day 4 | Change in Glycemia is measured as changes in blood glucose levels. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Triheptanoin (C7 Oil, Liquid) C7 oil was given at maximum tolerated dose (45% of total daily calories) to 10 Glut1 subjects receiving a ketogenic diet prior to enrolment as medically prescribed independently of this study. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Triheptanoin (C7 Oil, Liquid) |
|---|---|
| Age, Categorical <=18 years | 9 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 9 Participants |
| Region of Enrollment Argentina | 1 participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Ketosis (Beta-hydroxybutyrate Levels)
Change in Ketosis as measured by changes in blood beta-hydroxybutyric acid levels.
Time frame: Day 1, Day 4
Population: Subjects with Glut1 deficency
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketosis | Change in Ketosis (Beta-hydroxybutyrate Levels) | 3.82 mM | Standard Deviation 1.9 |
Secondary
Change in Glycemia
Change in Glycemia is measured as changes in blood glucose levels.
Time frame: Day 1 - Day 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketosis | Change in Glycemia | 81.2 mg/dl | Standard Deviation 13.6 |
Secondary
Fraction of Subjects (of a Total of 10 Studied) Who Exhibit a Change in Observable Seizure Rate
The percent change in observable seizure rate is measured as the change in observable seizure numbers from baseline to Day 4. Seizure rate is defined as count of seizures per patient per day.
Time frame: Baseline (Day 1) - Day 4
Population: All subjects with Glut1 deficiency studied. Triheptanoin (C7 oil, liquid). Subjects consumed triheptanoin 4 times over the course of one day. The approach included substituting a fraction of ketogenic diet fat with C7, weight by weight, at the maximum tolerable dose (45% of their their daily calories) in individuals receiving a ketogenic diet prior to enrolment prescribed independently of this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketosis | Fraction of Subjects (of a Total of 10 Studied) Who Exhibit a Change in Observable Seizure Rate | 3 Participants |