Treatment Development of Triheptanoin (G1D)

NCT ID: NCT03041363

Last Updated: 2022-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-29

Study Completion Date

2017-12-22

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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

TREATMENT

Blinding Strategy

NONE

Study Groups

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Triheptanoin

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

Group Type EXPERIMENTAL

Triheptanoin

Intervention Type DRUG

Triheptanoin will be administered for 7 days 4 times daily.

Interventions

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Triheptanoin

Triheptanoin will be administered for 7 days 4 times daily.

Intervention Type DRUG

Other Intervention Names

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C7

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Juan Pascual

OTHER

Sponsor Role lead

Responsible Party

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Juan Pascual

PROFESSOR

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Juan Pascual

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

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UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 25110966 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23072752 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26341673 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36859467 (View on PubMed)

Other Identifiers

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R01NS094257

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU 062016-105

Identifier Type: -

Identifier Source: org_study_id