Treatment Development of Triheptanoin (G1D)

Treatment Development of Triheptanoin (C7) for Glucose Transporter Type I Deficiency (G1D): A Phase I Maximum Tolerable Dose Trial

To determine the maximum tolerated dose (MTD), as a percentage of calories consumed, of triheptanoin (C7 oil; C7) in a pediatric and adult patient population genetically diagnosed with glucose transporter type 1 deficiency disorder (G1D).

The trial will use an open-label, standard 3+3 phase I design for determining the MTD of orally-administered C7 in G1D.

Triheptanoin: a triglyceride oil containing three odd-carbon chain-length fatty acids (i.e., a triglyceride of 7-carbon heptanoic acid). Triheptanoin will be taken 4 times per day (approximately every 6 hours) by mouth. it is dosed 4 times per day, divided evenly, and the total C7 daily dose will re-place 40% or 45% (depending on group) of the daily caloric intake from fat in the usual diet, based on current protocol guidelines. The oil should be taken approximately one hour before meals, and will be mixed with fat-free, sugar-free yogurt or pudding for administration.

Up to thirty-six subjects will be enrolled in a 10-day maximum tolerable dose trial of C7. Initiation of C7 dosing will be conducted in the Children's Medical Center Dallas ambulatory Care Pavilion neurology Clinic. Subjects will be provided with C7 oil to take over the 7 days of administration.

Subjects will not be required to stop other medications. Subjects will be directed to maintain their usual medications, including rescue seizure medications, as necessary for the course of the study. Subjects may have any clinical medical records transferred back to their referring physician at completion of the study.

Inclusion Criteria:

• Diagnosis of glucose transporter type I deficiency (G1D) confirmed by genotyping or PET scan of the brain.
• Stable on no dietary therapy other than Modified Atkins diet (i.e., on no dietary therapy for 1 month, including, but not limited to, medium chain triglyceride therapy).
• Males and females 2 years 6 months to 35 years 11 months old, inclusive.

Exclusion Criteria:

• Subjects with a history of life-threatening seizure episodes, including but not limited to status epilepticus and cardiac arrest.
• Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
• Subjects with a body mass index (BMI) greater than or equal to 30.
• Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, Crohn's disease, or colitis, which could increase the subject's risk of developing diarrhea or stomach pain.
• Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain triglyceride-supplemented diets, Atkins diet, low glycemic index diet, and related diets).
• 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 treatment with C7 one month prior to enrollment.
• Treatment with medium chain triglycerides in the last 30 days.
• 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 1 parent or legal guardian/representative to give written informed consent.