NCT03720665

Cortical Excitability Changes on the Sensorimotor Cortex Induced by Caffeine Consumption: A TMS Study

Completed NA Last updated 29 November 2019

What this trial tests

NA trial testing Caffeine_TMS in Cortical Excitability in 30 participants. Completed in 18 November 2019.

Timeline

1 October 2018

Primary endpoint
18 November 2019

18 November 2019

Quick facts

Lead sponsor	University Medical Center Goettingen
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	basic science
Enrollment	30
Start date	1 October 2018
Primary completion	18 November 2019
Estimated completion	18 November 2019
Sites	1 location across Germany

Drugs / interventions tested

• Caffeine_TMS

Conditions studied

• Cortical Excitability — all drugs for Cortical Excitability →
• Brain Stimulation — all drugs for Brain Stimulation →

Sponsor

University Medical Center Goettingen

Who can join

Adults 18 to 45, any sex, with Cortical Excitability or Brain Stimulation. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Caffeine is a widely used psychostimulant drug and acts as a competitive antagonist at adenosine receptors. Its effect is on neurons and glial cells of all brain areas. Chronic consumption of caffeine leads to tolerance which might be associated with an increased number of binding sites in the brain. In deep brain stimulation (DBS), the production of adenosine following the release of adenosine triphosphate (ATP) explains the reduction of in tremor. Binding of adenosine to adenosine A1 receptor suppresses excitatory transmission in the thalamus and thus reduces both tremor-and DBS-induced side effects. Also, the effect of adenosine was attenuated following the administration of the 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) adenosine A1 receptor antagonist. Therefore, the presence of a receptor antagonist such as caffeine was suggested to reduce the effectiveness of deep brain stimulation (DBS) in treating tremor and other movement disorders.

In light with this finding, we anticipate that the antagonistic effect of caffeine is a culprit to the reduction of effectiveness of any stimulation protocol in non-invasive stimulation (NIBS). In particular the excitatory effects of a NIBS protocol can tentatively be blocked in the presence of caffeine.

In this study, the effects of caffeine consumption on cortical excitability at the sensorimotor cortex shall be examined on focal and non-focal plasticity. Focal plasticity will be induced by paired associated stimulation (PAS) and global cortical plasticity from transcranial alternating current (tACS) stimulation. In case of tACS stimulation, 1) an excitatory protocol (tACS, 140 Hz, 1 mA) and 2) an inhibitory protocol (tACS, 140 Hz, 0.4 mA) with the active electrode over M1 and the return electrode over the orbitofrontal cortex will be used. Changes in cortical excitability are assessed using transcranial magnetic stimulation (TMS) recordings.

Research goals are to examine the effects of caffeine consumption on sensorimotor cortical excitability and stimulation induced plasticity. In addition, this study explores further factors which usually contribute to variability in cortical excitability studies. The results are expected to give a useful recommendation for researchers to reduce confounding factors and hereby improves repeatability.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Confounding effects of caffeine on neuroplasticity induced by transcranial alternating current stimulation and paired associative stimulation.
   Zulkifly MFM, Merkohitaj O, Brockmöller J, Paulus W. · · 2021 · cited 8× · PMID 33762129 · DOI 10.1016/j.clinph.2021.01.024
2. The roles of caffeine and corticosteroids in modulating cortical excitability after paired associative stimulation (PAS) and transcranial alternating current stimulation (tACS) in caffeine-naïve and caffeine-adapted subjects.
   Zulkifly MFM, Merkohitaj O, Paulus W, Brockmöller J. · · 2021 · cited 8× · PMID 33740589 · DOI 10.1016/j.psyneuen.2021.105201