Association Between Serum and Neuroimaging Measurements of the GABAergic System

The GABAergic System: Study of the Association Between Serum Measurements and Those Obtained Through Neuroimaging in Healthy Human Adults

The goal of this study is to better understand the relationship between peripheral and central nervous system measurements of the gamma-aminobutyric acid (GABA) system in otherwise healthy individuals. the main questions it aims to answer are:

1. Does GABA cross the blood-brain barrier?
2. Can peripheral measurements of the GABAergic system be used to study GABA in the brain?

Participants will receive oral GABA and Placebo and undergo blood draws, MRI scans and transcranial magnetic stimulation sessions.

Study Overview

• Status: Not yet recruiting
• Conditions: GABAergic System
• Intervention / Treatment: Other: Acute Oral gamma-aminobutyric acid (Natural Health Product in Canada); Other: Acute Placebo

Detailed Description

Although gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system in humans, and various pharmacological compounds and natural products aim to modulate it, it is still unknown whether GABA can cross the blood-brain barrier. The present project aims to clarify this issue by comparing measurements obtained in the central nervous system (the brain) with peripheral measurements (serum) following oral administration of the amino acid GABA. This will help determine if peripheral concentrations of GABA in the blood reflect levels in the brain. This would facility studying the GABAergic system in vulnerable clinical populations (such as children or patients with intellectual disabilities) to participate in without resorting to expensive neuroimaging exams and the inclusion of individuals who cannot undergo neuroimaging exams (e.g., claustrophobia, presence of metal in the body). To achieve this, GABA measurements (serum and neuroimaging) will be obtained before and after the oral intake of 1800mg of GABA or a placebo in 30 healthy adults participating in a cross-over, single-blind study with repeated measures.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: François Corbin, MD, Ph.D.; Phone Number: 15801 819-346-1110; Email: Francois.Corbin@USherbrooke.ca
• Study Contact Backup: Name: Samantha Cote, Ph.D.; Phone Number: 70184 819-346-1110; Email: Samantha.cote@usherbrooke.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Be between 18 and 35 years old
• Be of right manual dominance
• In good health

Exclusion Criteria:

• Have an implant or pacemaker,
• Having tinnitus,
• Have a history of fainting,
• Have already had an epileptic seizure or have a family history of epilepsy,
• Have a known neurological disease,
• Have a diagnosis of diabetes
• Be under psychotropic medication,
• Have suffered from substance abuse or dependence in the last 6 months,
• Have a neurostimulator,
• Have a splinter or metallic implant in the head or the rest of the body,
• Have a cochlear implant,
• Have an automated injection system implanted (insulin pump),
• Have a transdermal patch,
• Have tattoos in the area to be studied,
• Be pregnant or breastfeeding,
• Being claustrophobic or having other reasons that would prevent the volunteer from tolerating the imaging exam.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GABA Start Group; Participants who are randomly assigned to the GABA start group. These participants receive GABA at the first experimental visit and the placebo at the second experimental visit.	Other: Acute Oral gamma-aminobutyric acid (Natural Health Product in Canada); 1800 mg (3 capsules of 600mg) of GABA taken at the research center under the supervision of the research team.; Other Names: GABA; Other: Acute Placebo; A capsule filled with powdered sugar taken under the supervision of the research team.
Experimental: Placebo Start Group; Participants who are randomly assigned to the Placebo start group. These participants will receive a placebo at the first experimental visit and GABA at the second experimental visit.	Other: Acute Oral gamma-aminobutyric acid (Natural Health Product in Canada); 1800 mg (3 capsules of 600mg) of GABA taken at the research center under the supervision of the research team.; Other Names: GABA; Other: Acute Placebo; A capsule filled with powdered sugar taken under the supervision of the research team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of Acute GABA consumption on short intracortical inhibition	TMS-derived measure of Intracortical inhibition: The degree of decrease of peak-to-peak motor evoked potential (MEP) amplitude induced by the administration of a conditioning stimulus (set at 70% of resting motor threshold) 2-4 ms before the test stimulus (stimulation intensity required to produce an MEP of 1 millivolt (mV), approximately 120% of resting motor threshold)	Pre-GABA, 40 minutes after acute administration of GABA, Pre-Placebo, 40 minutes after acute administration of Placebo
Impact of Acute GABA consumption on peripheral serum GABA concentrations	Serum GABA concentration will be measured before and after acute administration of GABA and placebo.	Pre-GABA, 40 minutes after acute administration of GABA, Pre-Placebo, 40 minutes after acute administration of Placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of Acute GABA consumption on short intracortical facilitation	Transcranial magnetic stimulation (TMS) -derived measure of Intracortical facilitation: The degree of increase of peak-to-peak motor evoked potential (MEP) amplitude induced by the administration of a conditioning stimulus (set at 80% of resting motor threshold) 12-24 ms before the test stimulus (stimulation intensity required to produce an MEP of 1 mV, approximately 120% of resting motor threshold).	Pre-GABA, 40 minutes after acute administration of GABA, Pre-Placebo, 40 minutes after acute administration of Placebo
Impact of Acute GABA consumption on GABA concentrations in the brain	Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy	Pre-GABA, 40 minutes after acute administration of GABA, Pre-Placebo, 40 minutes after acute administration of Placebo
Impact of Acute GABA consumption on subjective alertness	Subjective alertness will be measured using the Biphasic Alcohol Alertness Scale (BAES). This scale which measures alertness and sedation and is comprised of 6 items, for each item participants rate how they feel from 1 (not at all) to 10 (extremely)	Pre-GABA, 40 minutes after acute administration of GABA, Pre-Placebo, 40 minutes after acute administration of Placebo
Impact of Acute GABA consumption on objective alertness	Objective alertness will be measured using the psychomotor vigilance task (PVT). This computerised task measures alertness, participants will have to respond to visual cues that are presented at random intervals on the screen.	Pre-GABA, 40 minutes after acute administration of GABA, Pre-Placebo, 40 minutes after acute administration of Placebo

Collaborators and Investigators

• Sponsor: Francois Corbin

Study record dates

Study Major Dates

• Study Start (Estimated): May 5, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Magnetic Resonance Spectroscopy; Neuroimaging; GABAergic system
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; GABA Agents; gamma-Aminobutyric Acid
• Other Study ID Numbers: 2024-5398 (Other Identifier: CÉR CIUSSS Estrie - CHUS)

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