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Cortical ExcitabilityNCT04011670

Neuroplastic Alterations of the Motor Cortex by Caffeine

A study testing 200 mg caffeine tablet and Non-active tablet in people with Cortical Excitability and Brain Stimulation, run by University Medical Center Goettingen at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Cortical Excitability, Brain Stimulation, Caffeine
What is being tested?
200 mg caffeine tablet and Non-active tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteGermany
Study dates
15 Jul 2019to 19 Nov 2019
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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's weight is above 60 kg

Who cannot join

  • Age < 18 or > 45 years old;
  • Left hand dominant;
  • Evidence of a chronic disease or history with a disorder of the nervous system
  • 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);
Show all 16Show fewer
  • 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
  • Breastfeeding
  • Intolerance to caffeine or coffee products
  • Participant who has abnormal heart activity from an electrocardiography (ECG) finding
  • Weight is less than 60 kg

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Prof. Dr. Walter Paulus

    Goettigen, Lower Saxony, 37075

Other trials in Germany

About this study

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

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.

Being tested
200 mg caffeine tablet, Non-active tablet
Keywords
Plasticity, Variability, Non-invasive brain stimulation, Caffeine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 200 mg caffeine tabletOther

    • 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 tabletOther

    • 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
Study groups in NCT04011670
Study groupRoleWhat they receive
Caffeine groupActive comparatorParticipants will receive a caffeine tablet and all electrical stimulations in a random order (tACS 140 Hz at 1 mA and sham tACS). Participant's vigilance status will be monitor based on active vigilance condition or passive vigilance condition.
Receives: Other: 200 mg caffeine tablet
Placebo groupPlacebo comparatorParticipants will receive a placebo tablet and all electrical stimulations in a random order (tACS 140 Hz at 1 mA and sham tACS). Participant's vigilance status will be monitor based on active vigilance condition or passive vigilance condition.
Receives: Other: Non-active tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes

  2. 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)

    Measured: 10 minutes

Secondary outcomes (1)
  1. Genetic polymorphism

    Brain-derived neurotrophic factor (BDNF) gene polymorphisms on cortical plasticity

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2019
  2. Study start15 Jul 2019
  3. Primary completion19 Nov 2019
  4. Study completion19 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
15 participants are assigned to caffeine group and another 15 are assigned to placebo group. Then, the participants who were initially in the caffeine group now be in placebo group and those who were in the placebo group were assigned to caffeine group. Finally, all participants received both placebo and caffeine
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04011670
Sponsor's protocol ID
33/3/19
Status last verified
Nov 2019
First submitted
21 May 2019
Last updated
29 Nov 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Antal A, Alekseichuk I, Bikson M, Brockmoller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Floel 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.

    PubMed 28709880
  • 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.

    PubMed 20965453
  • Biabani M, Farrell M, Zoghi M, Egan G, Jaberzadeh S. The minimal number of TMS trials required for the reliable assessment of corticospinal excitability, short interval intracortical inhibition, and intracortical facilitation. Neurosci Lett. 2018 May 1;674:94-100. doi: 10.1016/j.neulet.2018.03.026. Epub 2018 Mar 15.

    PubMed 29551425
  • 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.

    PubMed 26074744
  • 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):611. doi: 10.3390/nu10050611.

    PubMed 29757951
  • 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.

    PubMed 28264713
  • 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.

    PubMed 24475111
  • 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.

    PubMed 21713181
  • 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.

    PubMed 26872998
  • Hanajima R, Tanaka N, Tsutsumi R, Shirota Y, Shimizu T, Terao Y, Ugawa Y. Effect of caffeine on long-term potentiation-like effects induced by quadripulse transcranial magnetic stimulation. Exp Brain Res. 2019 Mar;237(3):647-651. doi: 10.1007/s00221-018-5450-9. Epub 2018 Dec 10.

    PubMed 30535949
  • Higdon JV, Frei B. Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr. 2006;46(2):101-23. doi: 10.1080/10408390500400009.

    PubMed 16507475
  • 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.

    PubMed 26050599
  • 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.

    PubMed 25241287
  • 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.

    PubMed 24103535
  • Marquez-Ruiz J, Leal-Campanario R, Sanchez-Campusano R, Molaee-Ardekani B, Wendling F, Miranda PC, Ruffini G, Gruart A, Delgado-Garcia 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.

    PubMed 22493252

Questions about this trial

What is this clinical trial studying?

A study testing 200 mg caffeine tablet and Non-active tablet in people with Cortical Excitability and Brain Stimulation, run by University Medical Center Goettingen at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neuroplastic changes of the cortical areas (time frame: Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04011670, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.

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