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

November 27, 2019 updated by: Prof. Dr. Walter Paulus, University Medical Center Goettingen

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Lower Saxony
      • Goettigen, Lower Saxony, Germany, 37075
        • Prof. Dr. Walter Paulus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Caffeine group
  • 200mg caffeine tablet
  • transcranial alternating current stimulation (140 Hz tACS) at 1 mA
  • transcranial alternating current stimulation (140 Hz tACS) at 0.4 mA
  • transcranial alternating current stimulation (140 Hz tACS) sham
  • paired associative stimulation (PAS 25)
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)]
PLACEBO_COMPARATOR: Placebo group
  • Non-active tablet
  • transcranial alternating current stimulation (140 Hz tACS) at 1 mA
  • transcranial alternating current stimulation (140 Hz tACS) at 0.4 mA
  • transcranial alternating current stimulation (140 Hz tACS) sham
  • paired associative stimulation (PAS 25)
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)]

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortical excitabiliy changes induced by caffeine consumption
Time Frame: Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 60 minutes
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain-derived neurotrophic factor (BDNF) gene polymorphisms on cortical plasticity
Time Frame: 3-6 months
Valine (Val) and Methionine (Met) alleles (i.e. Val66Met; Val66Val; Met66Met; Met66Val)
3-6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Goettingen

Investigators

  • Principal Investigator: Walter Paulus, Prof. Dr, University of Goettingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 1, 2018

Primary Completion (ACTUAL)

November 18, 2019

Study Completion (ACTUAL)

November 18, 2019

Study Registration Dates

First Submitted

October 24, 2018

First Submitted That Met QC Criteria

October 24, 2018

First Posted (ACTUAL)

October 25, 2018

Study Record Updates

Last Update Posted (ACTUAL)

November 29, 2019

Last Update Submitted That Met QC Criteria

November 27, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCGoettingen

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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