MRS Measurement of Glutamate and GABA Metabolism in Brain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00109174
Recruitment Status : Recruiting
First Posted : April 25, 2005
Last Update Posted : March 29, 2018
Information provided by:
National Institutes of Health Clinical Center (CC)

April 22, 2005
April 25, 2005
March 29, 2018
April 21, 2005
April 23, 2018   (Final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT00109174 on Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
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).

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.

Not Applicable
Primary Purpose: Treatment
Procedure: Magnetic Resonance Spectroscopy
To measure relative concentrations of 13C-labeled metabolites with Mass Spectroscopy technique
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
April 23, 2018
April 23, 2018   (Final data collection date for primary outcome measure)

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

Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
Contact: Maria D Ferraris Araneta, C.R.N.P. (301) 496-9423
Contact: Shizhe Steve Li, Ph.D. (301) 435-8859
United States
Not Provided
Not Provided
Not Provided
Not Provided
National Institute of Mental Health (NIMH)
Not Provided
Principal Investigator: Shizhe Steve Li, Ph.D. National Institute of Mental Health (NIMH)
National Institutes of Health Clinical Center (CC)
July 12, 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP