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

Cortical Excitability Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03720665
• Other study ID #: UMCGoettingen
• Status: Completed
• Phase: N/A
• Start date: October 1, 2018
• Est. completion date: November 18, 2019

Study information

• Verified date: November 2019
• Source: University Medical Center Goettingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 18, 2019
• Est. primary completion date: November 18, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Male and female healthy participants between the ages of 18-45.

• Right-handed (Oldfield 1971).

• Free willing participation and written, informed consent of all subjects obtained prior to the start of the study.

• Participant who willingly stop consuming caffeinated drinks at least three days before the experiment is performed

• Participant's weight is above 60 kg

Exclusion Criteria:

• Age < 18 or > 45 years old;

• Left hand dominant;

• Evidence of a chronic disease or residuals of a disorder of the nervous system in the history, in particular

• stroke

• History of epileptic seizures;

• Pacemaker or deep brain stimulation;

• Metal implants in the head region (metal used in the head region, for example, clips after the operation of an intracerebral aneurysm (vessel sacking in the region of the brain vessels), implantation of an artificial auditory canal);

• Cerebral trauma with loss of consciousness in prehistory;

• Existence of a serious internal (internal organs) or psychiatric (mental illness)

• Alcohol, medication or drug addiction;

• Receptive or global aphasia (disturbance of speech comprehension or additionally of speech);

• Participation in another scientific or clinical study within the last 4 weeks;

• Pregnancy

• Still period

• Participant who is unable to tolerate with caffeine or coffee products

• Participant who has abnormal heart activity from an electrocardiography (ECG) finding

• Weight is less than 60 kg

Related Conditions & MeSH terms

• Brain Stimulation
• Cortical Excitability

Intervention

Combination Product:
• Caffeine_TMS
Caffeine group: participants will receive a caffeine tablet and all electrical stimulations in a random order [transcranial electrical stimulation (tACS 140 Hz at 1 mA, 0.4 mA, sham) and paired associative stimulation (PAS 25)] Placebo tablet: participants will receive a placebo tablet and all electrical stimulations in a random order [transcranial electrical stimulation (tACS 140 Hz at 1 mA, 0.4 mA, sham) and paired associative stimulation (PAS 25)]

Locations

Country	Name	City	State
Germany	Prof. Dr. Walter Paulus	Goettigen	Lower Saxony

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Goettingen

Country where clinical trial is conducted

Germany, 

References & Publications (16)

Antal A, Alekseichuk I, Bikson M, Brockmöller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Flöel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19. Review. — View Citation

Bekar L, Libionka W, Tian GF, Xu Q, Torres A, Wang X, Lovatt D, Williams E, Takano T, Schnermann J, Bakos R, Nedergaard M. Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. Nat Med. 2008 Jan;14(1):75-80. Epub 2007 Dec 23. — View Citation

Cappelletti S, Piacentino D, Fineschi V, Frati P, Cipolloni L, Aromatario M. Caffeine-Related Deaths: Manner of Deaths and Categories at Risk. Nutrients. 2018 May 14;10(5). pii: E611. doi: 10.3390/nu10050611. Review. — View Citation

Cappelletti S, Piacentino D, Sani G, Aromatario M. Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015 Jan;13(1):71-88. doi: 10.2174/1570159X13666141210215655. Review. Erratum in: Curr Neuropharmacol. 2015;13(4):554. Daria, Piacentino [corrected to Piacentino, Daria]. — View Citation

Feurra M, Paulus W, Walsh V, Kanai R. Frequency specific modulation of human somatosensory cortex. Front Psychol. 2011 Feb 2;2:13. doi: 10.3389/fpsyg.2011.00013. eCollection 2011. — View Citation

Higdon JV, Frei B. Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr. 2006;46(2):101-23. Review. — View Citation

Márquez-Ruiz J, Leal-Campanario R, Sánchez-Campusano R, Molaee-Ardekani B, Wendling F, Miranda PC, Ruffini G, Gruart A, Delgado-García JM. Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6710-5. doi: 10.1073/pnas.1121147109. Epub 2012 Apr 9. — View Citation

Moliadze V, Antal A, Paulus W. Boosting brain excitability by transcranial high frequency stimulation in the ripple range. J Physiol. 2010 Dec 15;588(Pt 24):4891-904. doi: 10.1113/jphysiol.2010.196998. — View Citation

Moliadze V, Antal A, Paulus W. Electrode-distance dependent after-effects of transcranial direct and random noise stimulation with extracephalic reference electrodes. Clin Neurophysiol. 2010 Dec;121(12):2165-71. doi: 10.1016/j.clinph.2010.04.033. Epub 2010 Jun 15. — View Citation

Moliadze V, Atalay D, Antal A, Paulus W. Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. Brain Stimul. 2012 Oct;5(4):505-11. doi: 10.1016/j.brs.2011.11.004. Epub 2012 Feb 22. — View Citation

Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3:633-9. — View Citation

Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971 Mar;9(1):97-113. — View Citation

Polanía R, Nitsche MA, Korman C, Batsikadze G, Paulus W. The importance of timing in segregated theta phase-coupling for cognitive performance. Curr Biol. 2012 Jul 24;22(14):1314-8. doi: 10.1016/j.cub.2012.05.021. Epub 2012 Jun 7. — View Citation

Stefan K, Kunesch E, Benecke R, Cohen LG, Classen J. Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation. J Physiol. 2002 Sep 1;543(Pt 2):699-708. — View Citation

Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. Brain. 2000 Mar;123 Pt 3:572-84. — View Citation

Zaehle T, Rach S, Herrmann CS. Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One. 2010 Nov 1;5(11):e13766. doi: 10.1371/journal.pone.0013766. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cortical excitabiliy changes induced by caffeine consumption	Amplitude of motor evoked potential change (MEP)	Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 60 minutes
Secondary	Brain-derived neurotrophic factor (BDNF) gene polymorphisms on cortical plasticity	Valine (Val) and Methionine (Met) alleles (i.e. Val66Met; Val66Val; Met66Met; Met66Val)	3-6 months