NCT04031404

Glucose and Non-Invasive Brain Stimulation

Terminated NA Results posted Last updated 27 September 2021

What this trial tests

NA trial testing Single-pulse TMS in Glucose Metabolism Disorders in 23 participants. Terminated before completion.

Timeline

11 September 2019

Primary endpoint
31 August 2020

31 August 2020

Quick facts

Lead sponsor	University of North Carolina, Chapel Hill
Phase	NA
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	single
Primary purpose	basic science
Enrollment	23
Start date	11 September 2019
Primary completion	31 August 2020
Estimated completion	31 August 2020
Sites	1 location across United States

Drugs / interventions tested

• Single-pulse TMS

Conditions studied

• Glucose Metabolism Disorders — all drugs for Glucose Metabolism Disorders →

Sponsor

University of North Carolina, Chapel Hill

Who can join

Adults 18 to 65, any sex, with Glucose Metabolism Disorders. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Motor Evoked Potential (MEP) Primary · 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

MEP change (0 min vs pre-drink)

Group	Value	95% CI
MEP After Glucose Drink	0.14	± 0.15
MEP After Placebo Drink	-0.25	± 0.07

MEP change (30 min vs pre-drink)

Group	Value	95% CI
MEP After Glucose Drink	-0.02	± 0.19
MEP After Placebo Drink	-0.12	± 0.11

MEP change (60 min vs pre-drink)

Group	Value	95% CI
MEP After Glucose Drink	-0.08	± 0.14
MEP After Placebo Drink	-0.33	± 0.10

MEP change (120 min vs pre-drink)

Group	Value	95% CI
MEP After Glucose Drink	-0.05	± 0.16
MEP After Placebo Drink	-0.25	± 0.09

MEP change (180 min vs pre-drink)

Group	Value	95% CI
MEP After Glucose Drink	-0.21	± 0.18
MEP After Placebo Drink	-0.18	± 0.10

TMS Evoked Potential (TEP) Primary · 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 comp

TEP change (P25: 0 min vs pre-drink)

Group	Value	95% CI
Source-localized TEP After Glucose Drink	-0.04	± 0.08
Source-localized TEP After Placebo Drink	0.28	± 0.16

TEP change (P25: 30 min vs pre-drink)

Group	Value	95% CI
Source-localized TEP After Glucose Drink	-0.11	± 0.11
Source-localized TEP After Placebo Drink	0.024	± 0.05

TEP change (P25: 60 min vs pre-drink)

Group	Value	95% CI
Source-localized TEP After Glucose Drink	-0.16	± 0.11
Source-localized TEP After Placebo Drink	0.30	± 0.06

TEP change (P25: 120 min vs pre-drink)

Group	Value	95% CI
Source-localized TEP After Glucose Drink	-0.16	± 0.12
Source-localized TEP After Placebo Drink	0.24	± 0.07

TEP change (P25: 180 min vs pre-drink)

Group	Value	95% CI
Source-localized TEP After Glucose Drink	0.08	± 0.08
Source-localized TEP After Placebo Drink	0.02	± 0.15

EEG Measure of Alpha Asymmetry Oscillations Secondary · 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

Alpha Asymm. Change (0 min vs Baseline)

Group	Value	95% CI
Alpha Asymmetry After Glucose Drink	0.15	± 0.15
Alpha Asymmetry After Placebo Drink	0.59	± 0.45

Alpha Asymm. Change (30 min vs Baseline)

Group	Value	95% CI
Alpha Asymmetry After Glucose Drink	-0.01	± 0.20
Alpha Asymmetry After Placebo Drink	0.42	± 0.42

Alpha Asymm. Change (60 min vs Baseline)

Group	Value	95% CI
Alpha Asymmetry After Glucose Drink	0.14	± 0.22
Alpha Asymmetry After Placebo Drink	0.19	± 0.25

Alpha Asymm. Change (120 min vs Baseline)

Group	Value	95% CI
Alpha Asymmetry After Glucose Drink	0.18	± 0.22
Alpha Asymmetry After Placebo Drink	0.33	± 0.22

Alpha Asymm. Change (180 min vs Baseline)

Group	Value	95% CI
Alpha Asymmetry After Glucose Drink	0.18	± 0.33
Alpha Asymmetry After Placebo Drink	0.28	± 0.33

EEG Measure of Frontal Midline Theta Oscillations Secondary · 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

Theta Power Change (0 min vs Baseline)

Group	Value	95% CI
Midline Frontal Theta Oscillations After Glucose Drink	0.12	± 0.34
Midline Frontal Theta Oscillations After Placebo Drink	0.33	± 0.28

Theta Power Change (30 min vs Baseline)

Group	Value	95% CI
Midline Frontal Theta Oscillations After Glucose Drink	0.56	± 0.25
Midline Frontal Theta Oscillations After Placebo Drink	0.57	± 0.27

Theta Power Change (60 min vs Baseline)

Group	Value	95% CI
Midline Frontal Theta Oscillations After Glucose Drink	0.94	± 0.29
Midline Frontal Theta Oscillations After Placebo Drink	1.15	± 0.32

Theta Power Change (120 min vs Baseline)

Group	Value	95% CI
Midline Frontal Theta Oscillations After Glucose Drink	0.36	± 0.26
Midline Frontal Theta Oscillations After Placebo Drink	1.21	± 0.45

Theta Power Change (180 min vs Baseline)

Group	Value	95% CI
Midline Frontal Theta Oscillations After Glucose Drink	1.48	± 0.32
Midline Frontal Theta Oscillations After Placebo Drink	0.72	± 0.34

Working Memory Task Accuracy Secondary · 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

WM Accuracy (0 min vs Baseline)

Group	Value	95% CI
Working Memory Accuracy After Glucose Drink	1.02	± 0.03
Midline Frontal Theta Oscillations After Placebo Drink	0.97	± 0.03

WM Accuracy (30 min vs Baseline)

Group	Value	95% CI
Working Memory Accuracy After Glucose Drink	1.02	± 0.02
Midline Frontal Theta Oscillations After Placebo Drink	0.99	± 0.03

WM Accuracy (60 min vs Baseline)

Group	Value	95% CI
Working Memory Accuracy After Glucose Drink	1.06	± 0.02
Midline Frontal Theta Oscillations After Placebo Drink	1.01	± 0.03

WM Accuracy (120 min vs Baseline)

Group	Value	95% CI
Working Memory Accuracy After Glucose Drink	1.05	± 0.03
Midline Frontal Theta Oscillations After Placebo Drink	1.02	± 0.03

WM Accuracy (180 min vs Baseline)

Group	Value	95% CI
Working Memory Accuracy After Glucose Drink	1.03	± 0.03
Midline Frontal Theta Oscillations After Placebo Drink	1.03	± 0.03

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 2 months per participant. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TMS-EEG After Glucose Drink

Serious: 0/11 (0%)

Deaths: 0/11

TMS-EEG After Placebo Drink

Serious: 0/10 (0%)

Deaths: 0/10

Other adverse events (13 terms — click to expand)

Reaction	System	TMS-EEG After Glucose Drink	TMS-EEG After Placebo Drink
Sleepiness	General disorders	—	—
Headache	General disorders	—	—
Itching	Skin and subcutaneous tissue disorders	—	—
Worsening mood	Psychiatric disorders	—	—
Trouble concentrating	General disorders	—	—
Local redness	Skin and subcutaneous tissue disorders	—	—
Dizziness	General disorders	—	—
Scalp pain	Skin and subcutaneous tissue disorders	—	—
Ringing or buzzing noise	Ear and labyrinth disorders	—	—
Tingling	Skin and subcutaneous tissue disorders	—	—
Flickering lights	General disorders	—	—
Burning sensation	Skin and subcutaneous tissue disorders	—	—
Neck pain	Skin and subcutaneous tissue disorders	—	—

Data from ClinicalTrials.gov NCT04031404 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Causal role of frontal-midline theta in cognitive effort: a pilot study.
   McFerren A, Riddle J, Walker C, Buse JB, et al · · 2021 · cited 28× · PMID 34469696 · DOI 10.1152/jn.00068.2021