Clinical trial NCT04031404: Glucose and Non-Invasive Brain Stimulation
Official title: Modulation of Motor Cortex Excitability by Glucose Administration
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Glucose Metabolism Disorders
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-07-24
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Purpose: In this study, the investigators will delineate how brain network dynamics are modulated by experimentally induced elevated blood glucose levels and examine how glucose levels gate neuronal excitability measured by the response to TMS.

Participants: Participants must be between the ages of 18 and 65 with no known diabetes, no known adverse reaction to finger prick blood draw, and no known neurological or psychiatric illness. Participants must have a body-mass index less than 30.

Procedures: Participants will consume either a drink that contains 75 g of glucose or a placebo, and their response to TMS will be measured to examine the effect of glucose on motor cortex excitability.

Detailed description: This study will be a placebo-controlled study that investigates brain function with both electroencephalography (EEG) and TMS. On each study visit, a drink (either glucose drink or water) is administered after baseline assessment of fasting glucose. Changes in brain activity and excitability will be measured with resting-state EEG. Periodic high-density EEG of resting-state brain activity and activity during a working memory task will be performed before the administration of the drink, immediately after the administration of the drink, as well as 30 minutes, 60 minutes, 120 minutes, 150 minutes, and 180 minutes after the administration of the drink. The spectral content of the EEG signal will be investigated to identify the relative presence of cortical oscillations. Primarily, there will be a focus on theta (4-8 Hz) and alpha (8-12 Hz) oscillations.

Previous literature indicates that theta and alpha oscillations represent an engaged and disengaged cortical state, respectively \[1\]. Alpha and theta oscillations are implicated in cognitive function and are altered in depression. Therefore, this study aims to identify a decrease in frontal theta oscillations and an increase in left frontal alpha oscillations, two defining features of impaired top-down control and mood regulation, in response to the glucose drink contrasted with the response to the placebo.

The study will also examine how glucose levels gate neuronal excitability measured by the response to TMS. Cortical excitability will be measured by applying TMS pulses to the motor cortex and measuring the response in the form of a motor evoked potential by electromyography (EMG). TMS will be applied before the administration of the drink, immediately after the administration of the drink, as well as 30 minutes, 60 minutes, 120 minutes, 150 minutes, and 180 minutes after the administration of the drink. Changes in blood glucose will be monitored over this time interval as well.

Eligibility criteria: Inclusion Criteria:

* Right-handed
* BMI \<30
* Free of major neurological conditions and diabetes

Exclusion Criteria:

* Diabetes
* Adverse reaction to finger prick blood draw
* Known neurological or psychiatric illness
* Prior brain surgery
* Any brain devices/implants, including cochlear implants and aneurysm clips
* Cardiac pacemaker
* Any other implanted electronic device
* History of current traumatic brain injury
* Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study

Primary outcomes:
measure: Motor Evoked Potential (MEP)
timeFrame: Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
measure: TMS Evoked Potential (TEP)
timeFrame: Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
Secondary outcomes:
measure: EEG Measure of Alpha Asymmetry Oscillations
timeFrame: Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
measure: EEG Measure of Frontal Midline Theta Oscillations
timeFrame: Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
measure: Working Memory Task Accuracy
timeFrame: Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC Medical School Wing C
state: North Carolina
Study officials:
affiliation: Carolina Center for Neurostimulation
name: Flavio Frohlich
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stitt I, Zhou ZC, Radtke-Schuller S, Frohlich F. Arousal dependent modulation of thalamo-cortical functional interaction. Nat Commun. 2018 Jun 25;9(1):2455. doi: 10.1038/s41467-018-04785-6.