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MRS Measurement of Glutamate and GABA Metabolism in Brain

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 30, 2016 by National Institutes of Health Clinical Center (CC)
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: April 22, 2005
Last updated: April 20, 2017
Last verified: June 30, 2016
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).

Condition Intervention
Procedure: Magnetic Resonance Spectroscopy

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: MRS (Magnetic Resonance Spectroscopy) Measurement of Glutamate and GABA Metabolism in Brain

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 200
Study Start Date: April 20, 2005
Estimated Study Completion Date: January 23, 2018
Estimated Primary Completion Date: January 23, 2018 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Magnetic Resonance Spectroscopy
    To measure relative concentrations of 13C-labeled metabolites with Mass Spectroscopy technique
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.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Age: 18-65 years

Diagnosis: Healthy


Abnormal fasting blood glucose level (normal values are 70-115 mg/dL); All subjects must have a fasting blood glucose level of within the normal values of 70-115 mg/dL

Serious medical illness (including diabetes) as determined from H&P or laboratory testing; All subjects must meet none of the Axis I diagnoses

Prescription psychotropic medication; drug free period must be greater than 3 weeks for anticholinergics and benzodiazepine and greater than 8 weeks for fluoxetine, antipsychotics, anticonvulsants


Pregnancy; All women with child-bearing potential will have a blood and/or urine pregnancy test within 24 hours prior to the MRS study to exclude pregnancy

Any condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in the eye, etc.)

Unable to lay on one's back for MRI/MRS scans

Positive HIV test

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00109174

Contact: Maria D Ferraris Araneta, C.R.N.P. (301) 496-9423
Contact: Shizhe Steve Li, Ph.D. (301) 435-8859

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Principal Investigator: Shizhe Steve Li, Ph.D. National Institute of Mental Health (NIMH)