Not provided
Not provided
Not provided
Not provided
Not provided
COVID-19 Pandemic
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glucose drink followed by placebo | Experimental | Participants will consume the glucose drink at session 1, then they will consume the placebo (water) at session 2. |
|
| Placebo followed by glucose drink | Experimental | Participants will consume the placebo (water) at session 1, then they will consume the glucose drink at session 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Single-pulse TMS | Device | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Motor Evoked Potential (MEP) | Change in MEP over time to indicate changes in motor cortex excitability | 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. |
| TMS Evoked Potential (TEP) | 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. | 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 | Description | Time Frame |
|---|---|---|
| EEG Measure of Alpha Asymmetry Oscillations | Electroencephalography will be used to measure the change in lateralized alpha asymmetry (10-12 Hz electrical activity) over time | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Flavio Frohlich | Carolina Center for Neurostimulation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNC Medical School Wing C | Chapel Hill | North Carolina | 27514 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29941957 | Background | 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. |
Not provided
Not provided
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication.
IRB, IEC, or REB approval, as applicable, and execution of a data use/sharing agreement with UNC.
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Glucose Drink Followed by Placebo | 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). |
| FG001 | Placebo Followed by Glucose Drink | 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). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline |
|
| |||||||||||||||||||||
| Pre-randomization |
| ||||||||||||||||||||||
| First Drink Visit |
| ||||||||||||||||||||||
| Washout (5 Day Min) |
| ||||||||||||||||||||||
| Second Drink Visit |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Motor Evoked Potential (MEP) | Change in MEP over time to indicate changes in motor cortex excitability | 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. | Posted | Mean | Standard Error | log10(Post uV/Baseline uV) | 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. |
|
Up to 2 months per participant
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TMS-EEG After Glucose Drink | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ringing or buzzing noise | Ear and labyrinth disorders | Systematic Assessment |
The end sample sizes are lower than intended as the trial was ended early due to COVID-19-related research drawdowns. Technical limitations in the Electroencephalogram (EEG) and Transcranial Magnetic Stimulation (TMS) data collection resulted in N=1 and N=3 dataset to be excluded from final analyses, respectively.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rachel B. Force, PhD | University of North Carolina at Chapel Hill | 9199669929 | rachel_force@med.unc.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 3, 2020 | Apr 30, 2021 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
The researcher that interacts with the subject will not know whether the subject consumed the glucose drink or the placebo.
|
| EEG Measure of Frontal Midline Theta Oscillations |
Electroencephalography will be used to measure the change in frontal midline theta power (5-8 Hz electrical activity) over time |
| 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. |
| Working Memory Task Accuracy | 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. | 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. |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Participants receive TMS to motor cortex following consumption of a water control (~300 mL). |
|
|
| Primary | TMS Evoked Potential (TEP) | 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. | 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. | Posted | Mean | Standard Error | z-score | 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 | EEG Measure of Alpha Asymmetry Oscillations | Electroencephalography will be used to measure the change in lateralized alpha asymmetry (10-12 Hz electrical activity) over time | 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. | Posted | Mean | Standard Error | 10*log10(Right Alpha/Left Alpha) (uV) | 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 | EEG Measure of Frontal Midline Theta Oscillations | Electroencephalography will be used to measure the change in frontal midline theta power (5-8 Hz electrical activity) over time | 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. | Posted | Mean | Standard Error | 10*log10(Post uV/Baseline uV) | 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 | Working Memory Task Accuracy | 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. | 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. | Posted | Mean | Standard Error | Ratio of correct responses | 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. |
|
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 10 |
| 11 |
| EG001 | TMS-EEG After Placebo Drink | 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. | 0 | 10 | 0 | 10 | 8 | 10 |
| Dizziness | General disorders | Systematic Assessment |
|
| Sleepiness | General disorders | Systematic Assessment |
|
| Trouble concentrating | General disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Local redness | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Scalp pain | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Tingling | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Worsening mood | Psychiatric disorders | Systematic Assessment |
|
| Flickering lights | General disorders | Systematic Assessment |
|
| Burning sensation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Neck pain | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
| TEP change (P25: 30 min vs pre-drink) |
|
|
| TEP change (P25: 60 min vs pre-drink) |
|
|
| TEP change (P25: 120 min vs pre-drink) |
|
|
| TEP change (P25: 180 min vs pre-drink) |
|
|
| Alpha Asymm. Change (30 min vs Baseline) |
|
|
| Alpha Asymm. Change (60 min vs Baseline) |
|
|
| Alpha Asymm. Change (120 min vs Baseline) |
|
|
| Alpha Asymm. Change (180 min vs Baseline) |
|
|
| Theta Power Change (30 min vs Baseline) |
|
|
| Theta Power Change (60 min vs Baseline) |
|
|
| Theta Power Change (120 min vs Baseline) |
|
|
| Theta Power Change (180 min vs Baseline) |
|
|
| WM Accuracy (30 min vs Baseline) |
|
|
| WM Accuracy (60 min vs Baseline) |
|
|
| WM Accuracy (120 min vs Baseline) |
|
|
| WM Accuracy (180 min vs Baseline) |
|
|