Clinical trial NCT03181399: Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)
Official title: Dietary Treatment of Glucose Transporter Type 1 Deficiency (G1D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2017-06-08
Enrollment: 45
Sex: ALL
Minimum age (years): 24
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects will receive supplementation at the maximum tolerated dose.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Neuropsychological Score of Sustained Attention
timeFrame: Change post 6 months of treatment
measure: Neuropsychological Score of Sustained Attention
timeFrame: Change after 3 months off treatment
measure: Neuropsychological Score of Working Memory Index Scale (WMI)
timeFrame: Change post 6 months of treatment
measure: Neuropsychological Score of Working Memory Index Scale (WMI)
timeFrame: Change after 3 months off-treatment
measure: Neuropsychological Score of Processing Speed Index (PSI)
timeFrame: Change post 6 months of treatment
measure: Neuropsychological Score of Processing Speed Index (PSI)
timeFrame: Change after 3 months off-treatment
Secondary outcomes:
measure: EEG Changes: Generalized Spike Wave Activity and Burst
timeFrame: Change post 6 months of treatment
measure: EEG Changes: Generalized Spike Wave Activity and Burst
timeFrame: Change after 3 months off-treatment
measure: Brief Ataxia Rating Scale
timeFrame: Change post 6 months of treatment
measure: Brief Ataxia Rating Scale
timeFrame: Change after 3 months off treatment
measure: Clinical Global Impression Severity Scale
timeFrame: Change post 6 months of treatment
measure: Clinical Global Impression Severity Scale
timeFrame: Change after 3 months off-treatment
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: Study Principal Investigator
name: Juan Pascual, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.