MRS Measurement of Glutamate and GABA Metabolism in Brain
Study Overview
Detailed Description
13C is a stable (i.e., non-radioactive) isotope of carbon with a natural abundance of approximately 1%. Following infusion of [13C]glucose and/or [13C]acetate, in vivo MRS (magnetic resonance spectroscopy) can monitor the rate of flux of the 13C atom from glucose and/or acetate to glutamate to glutamine. Thus, this procedure can provide measure of glutamate (GLU) and glutamine (GLN) turnover in brain. We have established parameters to obtain these measurements in nonhuman primate brain. The current protocol seeks approval to optimize MRS parameters and to develop new MRS techniques for human brain using the GE 3T, the Siemens 3T, and the Siemens 7T device.
Study population: All subjects will be aged 18 - 65 years, without serious medical illnesses and meet criteria listed under 'Subjects'.
Design: Subjects will receive either oral administration of [13C]glucose or an intravenous infusion of [13C]glucose and/or [13C]acetate to approximately double their plasma glucose levels. The plasma acetate level will remain within the physiological range observed in humans. While lying in the 3T or 7T device, serial data acquisitions will be obtained over approximately 2 h to optimize the experimental conditions so as to measure the 13C signals from GLU, GLN and other metabolisms in brain.
Outcome measures: The primary goal of this study is to measure GLU/GLN turnover in brain. With no additional data acquisition, we can also obtain information on the synthesis of GABA, the major inhibitory neurotransmitter in brain. GLU is converted to GABA via the enzyme glutamic acid decarboxylase (GAD). While monitoring the transfer of 13C signal from GLU to GLN, we can simultaneously measure the transfer of 13C signal from GLU to GABA and thereby measure the activity of GAD. In addition to directly measure 13C signals, 13C labeling to brain metabolites can also be measured indirectly by detecting proton MRS during infusion of [13C]glucose and/or [13C]acetate.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Li An, Ph.D.
- Phone Number: (301) 896-2882
- Email: anl@mail.nih.gov
Study Contact Backup
- Name: Christopher S Johnson
- Phone Number: (301) 402-6695
- Email: johnsonchri@mail.nih.gov
Study Locations
-
-
Maryland
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Bethesda, Maryland, United States, 20892
- Recruiting
- National Institutes of Health Clinical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
- INCLUSION CRITERIA:
- 18-65 years of age
- Able to give written informed consent
- Healthy based on medical history and physical exam
- Enrolled in Protocol 01-M-0254 or Protocol 17-M-0181
EXCLUSION CRITERIA:
- Any current Axis 1 diagnosis
- Clinically significant laboratory abnormalities
- Positive HIV test
- Metallic foreign bodies that would be affected by the magnetic resonance imaging (MRI) magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.
- History of neurological illness or injury with the potential to affect study data interpretation, such as multiple sclerosis, Parkinson s disease, seizure disorder or traumatic brain injury
- Prescription psychotropic medication, drug free less than 8 weeks (anticholinergics, benzodiazepine, fluoxetine, antipsychotics, and anticonvulsants)
- Serious medical illness as determined from H&P or laboratory testing including Diabetes
- Inability to lie flat on camera bed for about two and a half hours
- Pregnant or breastfeeding
- Current substance use disorder based on DSM-5
- NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: One arm
Subjects receive the same test
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3T and 7T device
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
The primary outcome is the quality of the MR spectroscopy which includes spectrum signal-to-noise (SNR)\ ratio, spectral lineshape, linewidth, and resolution.
Time Frame: prospective and ongoing
|
To obtain more accurate and reliable MRS data from the human brain
|
prospective and ongoing
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
The secondary outcome is the performance improvements of the scanner hardware, software and methodology
Time Frame: prospective and ongoing
|
To obtain more accurate and reliable MRS data from the human brain.
|
prospective and ongoing
|
Collaborators and Investigators
Investigators
- Principal Investigator: Li An, Ph.D., National Institute of Mental Health (NIMH)
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 050144
- 05-M-0144
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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