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Treatment Development of Triheptanoin (G1D)

Primary Purpose

Epilepsy, GLUT1DS1, Glut1 Deficiency Syndrome 1, Autosomal Recessive

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Triheptanoin

About this trial

This is an interventional treatment trial for Epilepsy

Eligibility Criteria

2 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Triheptanoin

Arm Description

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose trial

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

Secondary Outcome Measures

Full Information

NCT ID

NCT03041363

First Posted

January 31, 2017

Last Updated

December 20, 2022

Sponsor

Juan Pascual

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT03041363

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

March 29, 2017 (Actual)

Primary Completion Date

December 22, 2017 (Actual)

Study Completion Date

December 22, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Juan Pascual

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Triheptanoin

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Triheptanoin

Other Intervention Name(s)

Intervention Description

Triheptanoin will be administered for 7 days 4 times daily.

Primary Outcome Measure Information:

Title

Maximum tolerated dose trial

Description

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

Time Frame

medication taken daily for 7 days.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juan Pascual

Organizational Affiliation

UT Southwestern Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25110966

Citation

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.

Results Reference

background

PubMed Identifier

23072752

Citation

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.

Results Reference

background

PubMed Identifier

26341673

Citation

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.

Results Reference

background

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Treatment Development of Triheptanoin (G1D)

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