Neuroplastic Alterations of the Motor Cortex by Caffeine

NCT ID: NCT04011670

Last Updated: 2019-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-15

Study Completion Date

2019-11-19

Brief Summary

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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.

Detailed Description

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Conditions

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Cortical Excitability Brain Stimulation Caffeine

Keywords

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Plasticity Variability Non-invasive brain stimulation Caffeine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators
A statistician prepares a randomization list. Only the pharmacist knows the medication type (caffeine or placebo) and the type of electrical stimulation. The researcher knows only the vigilance conditions (\*\*passive or \*active) . An investigator is blinded to the type of electrical stimulation and medication. In addition, all participants are naive to electrical stimulation and do not know if they receive placebo or verum drug.

Study Groups

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Caffeine group

Participants 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.

Group Type ACTIVE_COMPARATOR

200 mg caffeine tablet

Intervention Type OTHER

* 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

Placebo group

Participants 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.

Group Type PLACEBO_COMPARATOR

Non-active tablet

Intervention Type OTHER

* 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

Interventions

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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

Intervention Type OTHER

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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Medical Center Goettingen

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Walter Paulus

Head of Department for Clinical Neurophysiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Walter Paulus

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Goettingen, Goettingen

Locations

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Prof. Dr. Walter Paulus

Goettigen, Lower Saxony, Germany

Site Status

Countries

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Germany

References

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Zulkifly MFM, Merkohitaj O, Brockmoller J, Paulus W. Confounding effects of caffeine on neuroplasticity induced by transcranial alternating current stimulation and paired associative stimulation. Clin Neurophysiol. 2021 Jun;132(6):1367-1379. doi: 10.1016/j.clinph.2021.01.024. Epub 2021 Mar 10.

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Other Identifiers

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33/3/19

Identifier Type: -

Identifier Source: org_study_id