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Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)

Primary Purpose

GLUT1DS1, Epilepsy, Glut1 Deficiency Syndrome 1, Autosomal Recessive

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Triheptanoin

About this trial

This is an interventional treatment trial for GLUT1DS1

Eligibility Criteria

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

Inclusion Criteria:

Diagnosis of glucose transporter type I deficiency (G1D), confirmed by clinical genotyping at a CLIA-certified laboratory or by PET scan.
Stable diet on either a modified atkins diet or on no dietary therapy (i.e., no dietary therapy for 1 month).
Males and females 24 months to 35 years old, inclusive.

Exclusion Criteria:

Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, Crohn's disease, or colitis that could increase the subject's risk of developing diarrhea or stomach pain.
Subjects with a BMI (body mass index) greater than or equal to 30.
Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain triglyceride supplemented diets, Atkins diet, low glycemic index diet).
Subjects with no evidence of abnormal EEG (spike wave discharges) in the last 12 months.
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 use of triheptanoin in the past 1 month. Subjects who participate in Protocol 1 of this study are thus eligible.
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 subject or legal guardian/representative to give written informed consent, or assent for children age 10-17.
Addition of a new antiseizure drug in the previous 3 months.

Sites / Locations

University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Triheptanoin

Arm Description

This is a single arm study.

Outcomes

Primary Outcome Measures

Neuropsychological attention scores

To evaluate the impact of triheptanoin supplementation on measures of neuropsychological function primarily indicative of attention in G1D subjects receiving normal diet. These measures include one of two quantitative scales WPPSI-IV (Wechsler Preschool and Primary Scale of Intelligence; if younger than 7 years old), or WASI-II (Wechsler Abbreviated Scale of Intelligence; if older than 8 years old) depending on age.

Secondary Outcome Measures

EEG changes: spike-wave activity duration in EEG (electroencephalogram) tracings

Expecting to find a greater than 30% decrease in spike-wave activity determined as percent duration of spike-wave activity over the total duration of EEG.

Ataxia scores

Ataxia is scored 0 (normal; no ataxia) to 30 (severe ataxia) per modified ICARS ( International Cooperative Ataxia Rating Scale) scale in Schmahmann, J. D., Gardner, R., MacMore, J. and Vangel, M. G. (2009), Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS. Mov. Disord., 24: 1820-1828

Global impression scale

Scores range from 1 (very much improved) through to 7 (very much worse)

Full Information

NCT ID

NCT03181399

First Posted

April 25, 2017

Last Updated

April 28, 2023

Sponsor

University of Texas Southwestern Medical Center

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT03181399

Brief Title

Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)

Official Title

Dietary Treatment of Glucose Transporter Type 1 Deficiency (G1D)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 18, 2018 (Actual)

Primary Completion Date

September 30, 2023 (Anticipated)

Study Completion Date

September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Texas Southwestern Medical Center

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

Forty-five subjects receiving no dietary therapy with a proven G1D diagnosis will be enrolled. To evaluate the effect of C7 supplementation of a regular diet on a EEG activity in addition to IQ, language, working memory, processing speed, emotional and behavioral functioning, ataxia, and other neuropsychological and neurological performance indices in children and adults genetically diagnosed with G1D receiving a regular diet at enrollment.

Detailed Description

This is an open-label, single arm trial of orally-administered C7 in G1D. Subjects will replace a fixed percentage of their daily caloric intake (based on the results of Protocol 1) with C7 for 6 months, undergo full evaluation and discontinuation of treatment at a 6 month visit, and return for an off-treatment follow up visit 3 months after C7 oil discontinuation, for total duration of participation of 9 months. Subjects will undergo treatment initiation on a 24-hour inpatient basis. During that 24-hr inpatient treatment initiation, subjects will have continuous EEG both to monitor for real-time seizure activity (for safety) and to determine EEG changes (secondary outcome) before, during, and after treatment initiation. Subjects will undergo clinical evaluation, comprehensive blood work, ataxia scale rating, EEG, and neuropsychological testing at baseline, 6 months, and 9 months.

6. Conditions and Keywords

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

GLUT1DS1, Epilepsy, 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 2

Interventional Study Model

Single Group Assignment

Model Description

All subjects will receive supplementation at the maximum tolerated dose.

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Triheptanoin

Arm Type

Experimental

Arm Description

This is a single arm study.

Intervention Type

Drug

Intervention Name(s)

Triheptanoin

Other Intervention Name(s)

Intervention Description

. Triheptanoin will be taken 4 times per day (approximately every 6 hours: prior to breakfast, lunch and dinner and a mid-afternoon snack) by mouth. It is dosed 4 times per day, divided evenly.

Primary Outcome Measure Information:

Title

Neuropsychological attention scores

Description

Time Frame

Medication taken daily for 6 months.

Secondary Outcome Measure Information:

Title

EEG changes: spike-wave activity duration in EEG (electroencephalogram) tracings

Description

Expecting to find a greater than 30% decrease in spike-wave activity determined as percent duration of spike-wave activity over the total duration of EEG.

Time Frame

Medication taken daily for 6 months.

Title

Ataxia scores

Description

Time Frame

Medication taken daily for 6 months.

Title

Global impression scale

Description

Scores range from 1 (very much improved) through to 7 (very much worse)

Time Frame

Medication taken daily for 6 months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

24 Months

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of glucose transporter type I deficiency (G1D), confirmed by clinical genotyping at a CLIA-certified laboratory or by PET scan. Stable diet on either a modified atkins diet or on no dietary therapy (i.e., no dietary therapy for 1 month). Males and females 24 months to 35 years old, inclusive. Exclusion Criteria: Subjects with evidence of independent, unrelated metabolic and/or genetic disease. Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, Crohn's disease, or colitis that could increase the subject's risk of developing diarrhea or stomach pain. Subjects with a BMI (body mass index) greater than or equal to 30. Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain triglyceride supplemented diets, Atkins diet, low glycemic index diet). Subjects with no evidence of abnormal EEG (spike wave discharges) in the last 12 months. 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 use of triheptanoin in the past 1 month. Subjects who participate in Protocol 1 of this study are thus eligible. 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 subject or legal guardian/representative to give written informed consent, or assent for children age 10-17. Addition of a new antiseizure drug in the previous 3 months.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juan Pascual, MD

Organizational Affiliation

Study Principal Investigator

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas 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

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

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PubMed Identifier

28437535

Citation

Hao J, Kelly DI, Su J, Pascual JM. Clinical Aspects of Glucose Transporter Type 1 Deficiency: Information From a Global Registry. JAMA Neurol. 2017 Jun 1;74(6):727-732. doi: 10.1001/jamaneurol.2017.0298.

Results Reference

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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

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Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)

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