Neuroplastic Alterations of the Motor Cortex by Caffeine

Caffeine Clinical Trial

Official title:

Neuroplastic Alterations of the Motor Cortex by Caffeine: Differences Between Caffeine and Non-caffeine Users and Influence of Vigilance During Stimulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04011670
• Other study ID #: 33/3/19
• Status: Completed
• Phase: N/A
• Start date: July 15, 2019
• Est. completion date: November 19, 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 psychostimulant drug. It acts as a competitive antagonist at adenosine receptors, which modulate cortical excitability as well. In deep brain stimulation (DBS), the production of adenosine following the release of adenosine triphosphate (ATP) explains the reduction of tremor. Binding of adenosine to adenosine A1 receptors suppresses excitatory transmission in the thalamus and hereby 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.

Based on this finding, the investigators hypothesize that the antagonistic effect of caffeine can tentatively block the excitatory effects of transcranial alternating current stimulation (tACS). The plasticity effects might differ among caffeine users and non- caffeine users depending on the availability of receptor binding sites.

Apart from that, a major issue in NIBS studies including those studying motor-evoked potentials is the response variability both within and between individuals. The trial to trial variability of motor evoked potentials (MEPs) may be affected by many factors. Inherent to caffeine is its effect on vigilance. In this study, the investigator shall monitor the participant's vigilance by pupillometry to (1) better understand the factors, which might cause variability in transcranial excitability induction studies and (2) to separate the direct pharmacological effect from the indirect attentional effect of caffeine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 19, 2019
• Est. primary completion date: November 19, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

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

2. Right-handed (Oldfield 1971).

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

4. Participant's weight is above 60 kg

Exclusion Criteria:

1. Age < 18 or > 45 years old;

2. Left hand dominant;

3. Evidence of a chronic disease or history with a disorder of the nervous system

4. History of epileptic seizures;

5. Pacemaker or deep brain stimulation;

6. 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);

7. Cerebral trauma with loss of consciousness in prehistory;

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

9. Alcohol, medication or drug addiction;

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

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

12. Pregnancy

13. Breastfeeding

14. Intolerance to caffeine or coffee products

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

16. Weight is less than 60 kg

Related Conditions & MeSH terms

• Brain Stimulation
• Caffeine
• Cortical Excitability

Intervention

Other:
• 200 mg caffeine tablet
Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and passive vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and passive vigilance condition
• Non-active tablet
Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and passive vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and passive vigilance condition

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 (27)

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

Antal A, Chaieb L, Moliadze V, Monte-Silva K, Poreisz C, Thirugnanasambandam N, Nitsche MA, Shoukier M, Ludwig H, Paulus W. Brain-derived neurotrophic factor (BDNF) gene polymorphisms shape cortical plasticity in humans. Brain Stimul. 2010 Oct;3(4):230-7. doi: 10.1016/j.brs.2009.12.003. Epub 2010 Jan 14. — View Citation

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Cavaleri R, Schabrun SM, Chipchase LS. The number of stimuli required to reliably assess corticomotor excitability and primary motor cortical representations using transcranial magnetic stimulation (TMS): a systematic review and meta-analysis. Syst Rev. 2017 Mar 6;6(1):48. doi: 10.1186/s13643-017-0440-8. Review. — View Citation

Cuypers K, Thijs H, Meesen RL. Optimization of the transcranial magnetic stimulation protocol by defining a reliable estimate for corticospinal excitability. PLoS One. 2014 Jan 24;9(1):e86380. doi: 10.1371/journal.pone.0086380. eCollection 2014. — View Citation

Di Lazzaro V, Pellegrino G, Di Pino G, Corbetto M, Ranieri F, Brunelli N, Paolucci M, Bucossi S, Ventriglia MC, Brown P, Capone F. Val66Met BDNF gene polymorphism influences human motor cortex plasticity in acute stroke. Brain Stimul. 2015 Jan-Feb;8(1):92-6. doi: 10.1016/j.brs.2014.08.006. Epub 2014 Aug 23. — 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

Goldsworthy MR, Hordacre B, Ridding MC. Minimum number of trials required for within- and between-session reliability of TMS measures of corticospinal excitability. Neuroscience. 2016 Apr 21;320:205-9. doi: 10.1016/j.neuroscience.2016.02.012. Epub 2016 Feb 9. — View Citation

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Karabanov A, Ziemann U, Hamada M, George MS, Quartarone A, Classen J, Massimini M, Rothwell J, Siebner HR. Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation. Brain Stimul. 2015 May-Jun;8(3):442-54. doi: 10.1016/j.brs.2015.01.404. Epub 2015 Apr 1. Review. Corrected and republished in: Brain Stimul. 2015 Sep-Oct;8(5):993-1006. — View Citation

Lewis GN, Signal N, Taylor D. Reliability of lower limb motor evoked potentials in stroke and healthy populations: how many responses are needed? Clin Neurophysiol. 2014 Apr;125(4):748-754. doi: 10.1016/j.clinph.2013.07.029. Epub 2013 Oct 5. — 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

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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

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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

Ridding MC, Ziemann U. Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol. 2010 Jul 1;588(Pt 13):2291-304. doi: 10.1113/jphysiol.2010.190314. Epub 2010 May 17. Review. — View Citation

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuroplastic changes of the cortical areas	Motor cortex plasticity is measured from the changes in the amplitude of the motor evoked potentials (MEPs) at different time points. Transcranial magnetic stimulation (TMS) will be used to measure MEP amplitudes.	Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes
Primary	The influence of vigilance during stimulation	Participant's level of vigilance is monitored from pupil diameter and pupil unrest index (PUI) using pupillometer. This measurement is carried out during 10 minutes of transcranial alternating current stimulation (tACS)	10 minutes
Secondary	Genetic polymorphism	Brain-derived neurotrophic factor (BDNF) gene polymorphisms on cortical plasticity	1 year