Treatment Development of Triheptanoin (G1D)

• ClinicalTrials.gov Identifier: NCT03041363
• Recruitment Status: Completed
• First Posted: February 2, 2017
• Last Update Posted: December 22, 2022
• Sponsor: Juan Pascual
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Juan Pascual, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: January 31, 2017
• First Posted Date: February 2, 2017
• Last Update Posted Date: December 22, 2022
• Actual Study Start Date: March 29, 2017
• Actual Primary Completion Date: December 22, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2017)

Maximum tolerated dose trial [ Time Frame: medication taken daily for 7 days. ]

To determine the MTD as a percentage of calories consumed in pediatric and adult patient population.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment Development of Triheptanoin (G1D)
• Official Title: Treatment Development of Triheptanoin (C7) for Glucose Transporter Type I Deficiency (G1D): A Phase I Maximum Tolerable Dose Trial
• Brief Summary: 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).

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

The trial will use an open-label, standard 3+3 phase 1 design for determining the MTD of orally administered C7 in G1D.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Epilepsy
• GLUT1DS1
• Glut1 Deficiency Syndrome 1, Autosomal Recessive
• Glucose Metabolism Disorders
• Glucose Transport Defect
• Glucose Transporter Type 1 Deficiency Syndrome
• Glucose Transporter Protein Type 1 Deficiency Syndrome

Intervention

Drug: Triheptanoin

Triheptanoin will be administered for 7 days 4 times daily.

Other Name: C7

Study Arms

Experimental: Triheptanoin

Dose 1 C7 administered as 40% daily caloric intake. Dose 2. C7 administered as 45% daily caloric intake.

Intervention: Drug: Triheptanoin

Publications *

• Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.
• Marin-Valencia I, Good LB, Ma Q, Malloy CR, Pascual JM. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain. J Cereb Blood Flow Metab. 2013 Feb;33(2):175-82. doi: 10.1038/jcbfm.2012.151. Epub 2012 Oct 17.
• Pascual JM, Ronen GM. Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, Facts, and the Lives of Persons With This Rare Disease. Pediatr Neurol. 2015 Nov;53(5):379-93. doi: 10.1016/j.pediatrneurol.2015.08.001. Epub 2015 Aug 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 1, 2022): 12
• Original Estimated Enrollment (submitted: February 1, 2017): 36
• Actual Study Completion Date: December 22, 2017
• Actual Primary Completion Date: December 22, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 35 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03041363
• Other Study ID Numbers: STU 062016-105; R01NS094257 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Juan Pascual, University of Texas Southwestern Medical Center
• Original Responsible Party: University of Texas Southwestern Medical Center
• Current Study Sponsor: Juan Pascual
• Original Study Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Juan Pascual; UT Southwestern Medical Center

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: December 2022