Epilepsy, Glucose Metabolism Disorders, Glucose Transport Defect, Glucose Transporter Protein Type 1 Deficiency Syndrome, Glucose Transporter Type 1 Deficiency Syndrome, Glut1 Deficiency Syndrome 1, Glut1 Deficiency Syndrome 1, Autosomal Recessive
Conditions
Brief summary
The goal is to develop methodology to monitor flux in the citric acid cycle in brain via 13C nuclear magnetic resonance (NMR) spectroscopy at 7 Tesla or 3 Tesla.
Detailed description
The goal is to establish a protocol to 13C-label (from 13C-glucose) several physiological molecules: glucose, lactate, pyruvate and derived compounds. All of these molecules can undergo oxidation in the citric acid cycle. The intent is to study the 13C labeling pattern of these molecules in control and G1D subjects to determine if downstream products (such as 13C bicarbonate or 13C glutamate) due to oxidation in the mitochondria can be detected in brain or in blood by NMR analysis. While inside the instrument, the subjects may also undergo a 7T MR or 3T MR exam to correlate spectroscopy with brain structure.
Interventions
DEVICEMagnetic resonance imaging
Medical imaging technique used in radiology to form pictures of the anatomy.
Sponsors
Weill Medical College of Cornell University
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subjects will be adolescents or adults, age 16-80 years in good general health (evidenced by normal vital signs and no acute signs or symptoms of illness) or with previously (not for this study) documented G1D (genetically confirmed). 2. Ages 16 to 80 3. Persons with dental fillings, dental crowns, and short (max.4 cm) dental retainer wires can be included.
Exclusion criteria
1. People or patients with uncontrolled seizure disorder, defined as grand mal (not absence) seizure in the preceding 3 months. 2. Pregnant females will be excluded. A serum or urine pregnancy test will be administered to all females of child bearing potential within 24 hours of administration of the tracer and MRI scan. The pregnancy test will be communicated in person by the study PI. Positive results in subjects 17 years old or younger will be disclosed to parent/guardian only. 3. Subjects with typical implanted orthopedic metal in bone may be considered for inclusion in a 7T scan providing the implant is not within the volume of the radio frequency coil. The PI and the AIRC Medical Director will discuss each case and determine eligibility. 4. Persons with ICD, pacemakers, neurostimulators and other such devices will be excluded. 5. Persons with claustrophobia are excluded. 6. Persons with questionable ferrous implants, bullets, BB's, and shrapnel will be excluded. 7. Subjects who are not fluent in English will be excluded because immediate cooperation and the ability to respond to instructions from the investigators are necessary. 8. People following a ketogenic diet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Select metabolite abundance measured at 7Tfield strength | Day 1, immediately after 13 C labeled isotope infusion | Relative spectral amplitude at equilibrium time point (equilibrium will be defined from the spectra) of the lactate, glucose and bicarbonate spectral peaks arising from infused 13C glucose as measured by magnetic resonance spectroscopy (non contrast brain MRS 7T) |
| Select metabolite abundance measured at 3T field strength | Day 1, immediately after 13 C labeled isotope infusion | Relative spectral amplitude at equilibrium time point (equilibrium will be defined from the spectra) of the lactate, glucose and bicarbonate spectral peaks arising from infused 13C glucose as measured by magnetic resonance spectroscopy (non contrast brain MRS 3T) |
Countries
United States
Contacts
CONTACTJuan M Pascual, M.D.
CONTACTRocio Moron Ares, B.S.
Outcome results
None listed