Clinical trial NCT04011670: Neuroplastic Alterations of the Motor Cortex by Caffeine
Official title: Neuroplastic Alterations of the Motor Cortex by Caffeine: Differences Between Caffeine and Non-caffeine Users and Influence of Vigilance During Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cortical Excitability
Brain Stimulation
Caffeine
Keywords: Plasticity
Variability
Non-invasive brain stimulation
Caffeine
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
First posted: 2019-07-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Neuroplastic changes of the cortical areas
timeFrame: Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes
measure: The influence of vigilance during stimulation
timeFrame: 10 minutes
Secondary outcomes:
measure: Genetic polymorphism
timeFrame: 1 year
Other outcomes:
Locations:
city: Goettigen
country: Germany
facility: Prof. Dr. Walter Paulus
state: Lower Saxony
Study officials:
affiliation: University Medical Center Goettingen, Goettingen
name: Walter Paulus
role: PRINCIPAL_INVESTIGATOR
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