MRS Measurement of Glutamate and GABA Metabolism in Brain

MRS (Magnetic Resonance Spectroscopy) Measurement of Glutamate and GABA Metabolism in Brain

This study will use magnetic resonance spectroscopy (MRS) to measure in the brain the transfer of [13]C as it is naturally metabolized from glucose to specific chemical transmitters. From this method, we can measure the rate of production of an important excitatory neurotransmitter (glutamate) as well as an inhibitory neurotransmitter (GABA).

Study Overview

• Status: Recruiting
• Conditions: Normal Physiology
• Intervention / Treatment: Device: 3T and 7T device

Detailed Description

13C is a stable (i.e., non-radioactive) isotope of carbon with a natural abundance of ~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 in Section VI A.

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 (Lebon et al, 2002). While lying in the 3T or 7T device, serial data acquisitions will be obtained over ~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 (Li et al 2005). 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: Interventional
• Enrollment (Estimated): 200
• 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 Johnson; Phone Number: (301) 402-6695; Email: johnsonchri@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: One arm; Subjects receive the same test	Device: 3T and 7T device; 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.	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	To obtain more accurate and reliable MRS data from the human brain.	prospective and ongoing

Collaborators and Investigators

• Sponsor: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Li An, Ph.D., National Institute of Mental Health (NIMH)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2006
• Primary Completion (Estimated): January 11, 2030
• Study Completion (Estimated): March 11, 2030

Study Registration Dates

• First Submitted: April 22, 2005
• First Submitted That Met QC Criteria: April 22, 2005
• First Posted (Estimated): April 25, 2005

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 2, 2024

More Information

Terms related to this study

• Keywords: Brain; Glutamate; Magnetic Resonance Spectroscopy; Excitatory Amino Acid; Neurochemistry
• Other Study ID Numbers: 050144; 05-M-0144

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes