Glucose and Non-Invasive Brain Stimulation
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Glucose drink followed by placebo Participants will consume the glucose drink at session 1, then they will consume the placebo (water) at session 2. |
Device: Single-pulse TMS
Single-pulse transcranial magnetic stimulation (TMS) on the motor cortex will lead to a twitch in the target muscle and evoke a motor-evoked potential (MEP) measured by electromyography (EMG).
Other Names:
|
Experimental: Placebo followed by glucose drink Participants will consume the placebo (water) at session 1, then they will consume the glucose drink at session 2. |
Device: Single-pulse TMS
Single-pulse transcranial magnetic stimulation (TMS) on the motor cortex will lead to a twitch in the target muscle and evoke a motor-evoked potential (MEP) measured by electromyography (EMG).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Motor Evoked Potential (MEP) [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.]
Change in MEP over time to indicate changes in motor cortex excitability
- TMS Evoked Potential (TEP) [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.]
The TMS Evoked Potential (TEP) is the difference in microvolts from 25 milliseconds after a TMS pulse versus pre-TMS such that greater values indicate greater motor cortex excitability. The measure of the change in TEP over time since either glucose or water was consumed approximates a z-distribution with a range of -20 to 20 with central distribution measures of zero. TEPs were source localized and reported using a pseudo-neural activity index (PNAI) expressing source activation in relation to pre-TMS pulse trial baseline. The difference in the source peaks corresponding to the early P25 component have been reported as differences from baseline. Higher values indicate greater cortical excitation, consistent with the study hypothesis.
Secondary Outcome Measures
- EEG Measure of Alpha Asymmetry Oscillations [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.]
Electroencephalography will be used to measure the change in lateralized alpha asymmetry (10-12 Hz electrical activity) over time
- EEG Measure of Frontal Midline Theta Oscillations [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.]
Electroencephalography will be used to measure the change in frontal midline theta power (5-8 Hz electrical activity) over time
- Working Memory Task Accuracy [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.]
This outcome will analyze the change in accuracy in a computerized working memory task over time. During the task, subjects will be presented with an array of colored squares. Then, they will need to hold this array in mind during a delay period. Finally, participants will be tested on their memory of the array by responding whether a presented color is the same or different as the corresponding square in the first array. Participants' accuracy will be expressed as the percentage of correct responses (from 0% correct responses to 100% correct responses). An accuracy rate of 50% indicates that the participant is performing at the same accuracy level as random chance.
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UNC Medical School Wing C | Chapel Hill | North Carolina | United States | 27514 |
Sponsors and Collaborators
- University of North Carolina, Chapel Hill
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Flavio Frohlich, Carolina Center for Neurostimulation
Study Documents (Full-Text)
More Information
Publications
- 19-1451
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Glucose Drink Followed by Placebo | Placebo Followed by Glucose Drink |
---|---|---|
Arm/Group Description | Participants will consume the glucose drink at session 1, then they will consume the placebo (water) at session 2. Single-pulse TMS: Single-pulse transcranial magnetic stimulation (TMS) on the motor cortex will lead to a twitch in the target muscle and evoke a motor-evoked potential (MEP) measured by electromyography (EMG). | Participants will consume the placebo (water) at session 1, then they will consume the glucose drink at session 2. Single-pulse TMS: Single-pulse transcranial magnetic stimulation (TMS) on the motor cortex will lead to a twitch in the target muscle and evoke a motor-evoked potential (MEP) measured by electromyography (EMG). |
Period Title: Baseline | ||
STARTED | 10 | 13 |
COMPLETED | 8 | 8 |
NOT COMPLETED | 2 | 5 |
Period Title: Baseline | ||
STARTED | 8 | 8 |
COMPLETED | 6 | 5 |
NOT COMPLETED | 2 | 3 |
Period Title: Baseline | ||
STARTED | 6 | 5 |
COMPLETED | 6 | 5 |
NOT COMPLETED | 0 | 0 |
Period Title: Baseline | ||
STARTED | 6 | 5 |
COMPLETED | 5 | 5 |
NOT COMPLETED | 1 | 0 |
Period Title: Baseline | ||
STARTED | 5 | 5 |
COMPLETED | 5 | 5 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | All Participants |
---|---|
Arm/Group Description | Participants will consume the glucose drink at session 1, then they will consume the placebo (water) at session 2, or vice versa. Single-pulse TMS: Single-pulse transcranial magnetic stimulation (TMS) on the motor cortex will lead to a twitch in the target muscle and evoke a motor-evoked potential (MEP) measured by electromyography (EMG). |
Overall Participants | 23 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
23
100%
|
>=65 years |
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
24.64
(10.49)
|
Sex: Female, Male (Count of Participants) | |
Female |
15
65.2%
|
Male |
8
34.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
1
4.3%
|
Not Hispanic or Latino |
21
91.3%
|
Unknown or Not Reported |
1
4.3%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
5
21.7%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
4
17.4%
|
White |
13
56.5%
|
More than one race |
1
4.3%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (Count of Participants) | |
United States |
23
100%
|
Outcome Measures
Title | Motor Evoked Potential (MEP) |
---|---|
Description | Change in MEP over time to indicate changes in motor cortex excitability |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
From the 10 participants who completed, 3 were excluded from the analysis due to technical reasons. Two participants had to end their glucose visits early due to scheduling conflicts. The reported N below is adjusted where appropriate. |
Arm/Group Title | MEP After Glucose Drink | MEP After Placebo Drink |
---|---|---|
Arm/Group Description | Participants receive TMS to motor cortex following consumption of a 75 g glucose drink (~300 mL). | Participants receive TMS to motor cortex following consumption of a water control (~300 mL). |
Measure Participants | 7 | 7 |
MEP change (0 min vs pre-drink) |
0.14
(0.15)
|
-0.25
(0.07)
|
MEP change (30 min vs pre-drink) |
-0.02
(0.19)
|
-0.12
(0.11)
|
MEP change (60 min vs pre-drink) |
-0.08
(0.14)
|
-0.33
(0.10)
|
MEP change (120 min vs pre-drink) |
-0.05
(0.16)
|
-0.25
(0.09)
|
MEP change (180 min vs pre-drink) |
-0.21
(0.18)
|
-0.18
(0.10)
|
Title | TMS Evoked Potential (TEP) |
---|---|
Description | The TMS Evoked Potential (TEP) is the difference in microvolts from 25 milliseconds after a TMS pulse versus pre-TMS such that greater values indicate greater motor cortex excitability. The measure of the change in TEP over time since either glucose or water was consumed approximates a z-distribution with a range of -20 to 20 with central distribution measures of zero. TEPs were source localized and reported using a pseudo-neural activity index (PNAI) expressing source activation in relation to pre-TMS pulse trial baseline. The difference in the source peaks corresponding to the early P25 component have been reported as differences from baseline. Higher values indicate greater cortical excitation, consistent with the study hypothesis. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
From the 10 participants who completed, 3 were excluded from the analysis due to technical reasons. Two participants had to end their glucose visits early due to scheduling conflicts. The reported N below is adjusted where appropriate. |
Arm/Group Title | Source-localized TEP After Glucose Drink | Source-localized TEP After Placebo Drink |
---|---|---|
Arm/Group Description | Participants receive TMS to motor cortex following consumption of a 75 g glucose drink (~300 mL). | Participants receive TMS to motor cortex following consumption of a water control (~300 mL). |
Measure Participants | 7 | 7 |
TEP change (P25: 0 min vs pre-drink) |
-0.04
(0.08)
|
0.28
(0.16)
|
TEP change (P25: 30 min vs pre-drink) |
-0.11
(0.11)
|
0.024
(0.05)
|
TEP change (P25: 60 min vs pre-drink) |
-0.16
(0.11)
|
0.30
(0.06)
|
TEP change (P25: 120 min vs pre-drink) |
-0.16
(0.12)
|
0.24
(0.07)
|
TEP change (P25: 180 min vs pre-drink) |
0.08
(0.08)
|
0.02
(0.15)
|
Title | EEG Measure of Alpha Asymmetry Oscillations |
---|---|
Description | Electroencephalography will be used to measure the change in lateralized alpha asymmetry (10-12 Hz electrical activity) over time |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
From the 10 participants who completed, one was excluded from the analysis due to technical reasons. Two participants had to end their glucose visits early due to scheduling conflicts. The reported N below is adjusted where appropriate. |
Arm/Group Title | Alpha Asymmetry After Glucose Drink | Alpha Asymmetry After Placebo Drink |
---|---|---|
Arm/Group Description | Participants complete a resting state EEG recording following consumption of a 75 g glucose drink (~300 mL). | Participants complete a resting state EEG recording following consumption of a 75 g glucose drink (~300 mL). |
Measure Participants | 9 | 9 |
Alpha Asymm. Change (0 min vs Baseline) |
0.15
(0.15)
|
0.59
(0.45)
|
Alpha Asymm. Change (30 min vs Baseline) |
-0.01
(0.20)
|
0.42
(0.42)
|
Alpha Asymm. Change (60 min vs Baseline) |
0.14
(0.22)
|
0.19
(0.25)
|
Alpha Asymm. Change (120 min vs Baseline) |
0.18
(0.22)
|
0.33
(0.22)
|
Alpha Asymm. Change (180 min vs Baseline) |
0.18
(0.33)
|
0.28
(0.33)
|
Title | EEG Measure of Frontal Midline Theta Oscillations |
---|---|
Description | Electroencephalography will be used to measure the change in frontal midline theta power (5-8 Hz electrical activity) over time |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
From the 10 participants who completed, one was excluded from the analysis due to technical reasons. Two participants had to end their glucose visits early due to scheduling conflicts. The reported N below is adjusted where appropriate. |
Arm/Group Title | Midline Frontal Theta Oscillations After Glucose Drink | Midline Frontal Theta Oscillations After Placebo Drink |
---|---|---|
Arm/Group Description | Participants complete a resting state EEG recording following consumption of a 75 g glucose drink (~300 mL). | Participants complete a resting state EEG recording following consumption of a 75 g glucose drink (~300 mL). |
Measure Participants | 9 | 9 |
Theta Power Change (0 min vs Baseline) |
0.12
(0.34)
|
0.33
(0.28)
|
Theta Power Change (30 min vs Baseline) |
0.56
(0.25)
|
0.57
(0.27)
|
Theta Power Change (60 min vs Baseline) |
0.94
(0.29)
|
1.15
(0.32)
|
Theta Power Change (120 min vs Baseline) |
0.36
(0.26)
|
1.21
(0.45)
|
Theta Power Change (180 min vs Baseline) |
1.48
(0.32)
|
0.72
(0.34)
|
Title | Working Memory Task Accuracy |
---|---|
Description | This outcome will analyze the change in accuracy in a computerized working memory task over time. During the task, subjects will be presented with an array of colored squares. Then, they will need to hold this array in mind during a delay period. Finally, participants will be tested on their memory of the array by responding whether a presented color is the same or different as the corresponding square in the first array. Participants' accuracy will be expressed as the percentage of correct responses (from 0% correct responses to 100% correct responses). An accuracy rate of 50% indicates that the participant is performing at the same accuracy level as random chance. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
From the 10 participants who completed, one was excluded from the analysis due to technical reasons. Two participants had to end their glucose visits early due to scheduling conflicts. The reported N below is adjusted where appropriate. |
Arm/Group Title | Working Memory Accuracy After Glucose Drink | Midline Frontal Theta Oscillations After Placebo Drink |
---|---|---|
Arm/Group Description | Participants complete a working memory task following consumption of a 75 g glucose drink (~300 mL). | Participants complete a working memory task recording following consumption of a 75 g glucose drink (~300 mL). |
Measure Participants | 9 | 9 |
WM Accuracy (0 min vs Baseline) |
1.02
(0.03)
|
0.97
(0.03)
|
WM Accuracy (30 min vs Baseline) |
1.02
(0.02)
|
0.99
(0.03)
|
WM Accuracy (60 min vs Baseline) |
1.06
(0.02)
|
1.01
(0.03)
|
WM Accuracy (120 min vs Baseline) |
1.05
(0.03)
|
1.02
(0.03)
|
WM Accuracy (180 min vs Baseline) |
1.03
(0.03)
|
1.03
(0.03)
|
Adverse Events
Time Frame | Up to 2 months per participant | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | TMS-EEG After Glucose Drink | TMS-EEG After Placebo Drink | ||
Arm/Group Description | Participants receive TMS to motor cortex following consumption of a 75 g glucose drink (~300 mL). During every session, participants receive single pulse TMS to the motor cortex, and complete EEG recordings and a working memory task at several time points. | Participants receive TMS to motor cortex following consumption of a water control drink (~300 mL). During every session, participants receive single pulse TMS to the motor cortex, and complete EEG recordings and a working memory task at several time points. | ||
All Cause Mortality |
||||
TMS-EEG After Glucose Drink | TMS-EEG After Placebo Drink | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/11 (0%) | 0/10 (0%) | ||
Serious Adverse Events |
||||
TMS-EEG After Glucose Drink | TMS-EEG After Placebo Drink | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/11 (0%) | 0/10 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
TMS-EEG After Glucose Drink | TMS-EEG After Placebo Drink | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/11 (90.9%) | 8/10 (80%) | ||
Ear and labyrinth disorders | ||||
Ringing or buzzing noise | 2/11 (18.2%) | 2 | 0/10 (0%) | 0 |
General disorders | ||||
Dizziness | 3/11 (27.3%) | 3 | 1/10 (10%) | 1 |
Sleepiness | 8/11 (72.7%) | 8 | 5/10 (50%) | 5 |
Trouble concentrating | 4/11 (36.4%) | 4 | 2/10 (20%) | 2 |
Headache | 5/11 (45.5%) | 5 | 3/10 (30%) | 3 |
Flickering lights | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
Psychiatric disorders | ||||
Worsening mood | 5/11 (45.5%) | 5 | 2/10 (20%) | 2 |
Skin and subcutaneous tissue disorders | ||||
Itching | 5/11 (45.5%) | 5 | 4/10 (40%) | 4 |
Local redness | 4/11 (36.4%) | 4 | 1/10 (10%) | 1 |
Scalp pain | 3/11 (27.3%) | 3 | 3/10 (30%) | 3 |
Tingling | 2/11 (18.2%) | 2 | 1/10 (10%) | 1 |
Burning sensation | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
Neck pain | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Rachel B. Force, PhD |
---|---|
Organization | University of North Carolina at Chapel Hill |
Phone | 9199669929 |
rachel_force@med.unc.edu |
- 19-1451