Treatment Development of Triheptanoin (G1D)

NCT03041363 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: STU 062016-105R01NS094257
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose trial

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

  medication taken daily for 7 days.

Study Arms (1)

Triheptanoin

EXPERIMENTAL

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

Drug: Triheptanoin

Interventions

Triheptanoin DRUG

Triheptanoin will be administered for 7 days 4 times daily.

Also known as: C7

Triheptanoin

Eligibility Criteria

• Age: 2 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Juan Pascual: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (4)

• 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.

  PMID: 25110966 BACKGROUND

• 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.

  PMID: 23072752 BACKGROUND

• 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.

  PMID: 26341673 BACKGROUND

• Malaga I, Avila A, Primeaux S, Kallem RR, Roe CR, Putnam WC, Park JY, Shinnar S, Ahn C, Pascual JM. Maximum dose, safety, tolerability and ketonemia after triheptanoin in glucose transporter type 1 deficiency (G1D). Sci Rep. 2023 Mar 1;13(1):3465. doi: 10.1038/s41598-023-30578-z.

  PMID: 36859467 DERIVED

MeSH Terms

Conditions

Epilepsy; Glucose Metabolism Disorders; Glycogen Storage Disease Id; Glut1 Deficiency Syndrome

Interventions

triheptanoin

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Juan Pascual

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PROFESSOR

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

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: February 2, 2017
• Study Start: March 29, 2017
• Primary Completion: December 22, 2017
• Study Completion: December 22, 2017
• Last Updated: December 22, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)