Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Triheptanoin This is a single arm study. |
Drug: Triheptanoin
. 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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Neuropsychological attention scores [Medication taken daily for 6 months.]
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 [Medication taken daily for 6 months.]
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 [Medication taken daily for 6 months.]
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 [Medication taken daily for 6 months.]
Scores range from 1 (very much improved) through to 7 (very much worse)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of glucose transporter type I deficiency (G1D), confirmed by clinical genotyping at a CLIA-certified laboratory or by PET scan.
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Stable diet on either a modified atkins diet or on no dietary therapy (i.e., no dietary therapy for 1 month).
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Males and females 24 months to 35 years old, inclusive.
Exclusion Criteria:
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Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
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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.
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Subjects with a BMI (body mass index) greater than or equal to 30.
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Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain triglyceride supplemented diets, Atkins diet, low glycemic index diet).
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Subjects with no evidence of abnormal EEG (spike wave discharges) in the last 12 months.
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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.
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Allergy/sensitivity to C7.
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Previous use of triheptanoin in the past 1 month. Subjects who participate in Protocol 1 of this study are thus eligible.
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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.
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Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
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Inability or unwillingness of subject or legal guardian/representative to give written informed consent, or assent for children age 10-17.
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Addition of a new antiseizure drug in the previous 3 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
- National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
- Principal Investigator: Juan Pascual, MD, Study Principal Investigator
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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. Review.
- 122016-013
- 1R01NS094257-01A1