Brain Metabolism Observed at 3 Tesla or 7 Tesla in Health and Metabolic Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Glucose Metabolism Disorders; Epilepsy; Glucose Transporter Type 1 Deficiency Syndrome; Glut1 Deficiency Syndrome 1; Glut1 Deficiency Syndrome 1, Autosomal Recessive; Glucose Transporter Protein Type 1 Deficiency Syndrome; Glucose Transport Defect
• Intervention / Treatment: Device: Magnetic resonance imaging

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.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Juan M Pascual, M.D.; Phone Number: 212 746 3278; Email: jup9003@med.cornell.edu
• Study Contact Backup: Name: Rocio Moron Ares, B.S.; Phone Number: 212 746 3278; Email: rrm4007@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Contact: Rocio Moron Ares, B.S.; Phone Number: 212 746 3278; Email: rrm4007@med.cornell.edu
      • Contact: Juan M Pascual, M.D; Phone Number: 212 746 3278; Email: jup9003@med.cornell.edu
  • Texas
    • Dallas, Texas, United States, 75390
      • Terminated
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adolescents and adults with Glut1 Deficiency; Normal, healthy adolescents and adults.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adolescents and adults with Glut1 deficiency	Device: Magnetic resonance imaging; Medical imaging technique used in radiology to form pictures of the anatomy.; Other Names: MRI
Normal healthy adolescents and adults	Device: Magnetic resonance imaging; Medical imaging technique used in radiology to form pictures of the anatomy.; Other Names: MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Select metabolite abundance measured at 7Tfield strength	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)	Day 1, immediately after 13 C labeled isotope infusion
Select metabolite abundance measured at 3T field strength	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)	Day 1, immediately after 13 C labeled isotope infusion

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2022
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Epilepsy; Glucose Metabolism Disorders; Glut1 Deficiency Syndrome; Glycogen Storage Disease Id; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Magnetic Resonance Imaging
• Other Study ID Numbers: 24-08027788; RM1NS133593 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No