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Modulating Pain Using Transcranial Alternating Stimulation (tACS) in Healthy Human Subjects

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ClinicalTrials.gov Identifier: NCT03805854
Recruitment Status : Recruiting
First Posted : January 16, 2019
Last Update Posted : April 10, 2019
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Markus Ploner, Technische Universität München

Brief Summary:
Pain is a highly complex and subjective phenomenon which results from the dynamic integration of sensory and contextual (i.e. cognitive, emotional, and motivational) processes. Recent evidence suggests that neural oscillations and their synchronization between different brain areas might form the basis of these integrative functions. When investigating tonic experimental pain lasting for several minutes, for example, objective stimulus intensity is inversely related to alpha (8-13 Hz) and beta (13-30 Hz) oscillations in early somatosensory areas, while subjective pain intensity is positively associated with gamma (30-100 Hz) oscillations in prefrontal cortex. Yet, with a few exemptions, reported links between oscillatory brain activity and pain have mostly been established by correlative approaches which do not allow to infer causality. The current project aims at comprehensively investigating the causal role of neural oscillations for tonic experimental pain in healthy human subjects. To this end, transcranial alternating current stimulation (tACS) will be employed to modulate oscillatory brain activity in alpha and gamma frequency bands and investigate effects of this manipulation on pain perception and pain-related autonomic responses. Using an established tonic pain stimulation protocol and a double-blind, sham-controlled design, effects of tACS of somatosensory as well as prefrontal brain areas will be investigated. Results promise to elucidate the neural mechanisms underlying tonic experimental pain by testing the mechanistic role of neural oscillations in different aspects of pain processing. Furthermore, they might contribute to the development of urgently needed new treatment approaches for chronic pain using neuromodulatory methods.

Condition or disease Intervention/treatment Phase
Experimental Pain in Healthy Human Subjects Device: 10 Hz tACS of the bilateral somatosensory cortex Device: 10 Hz tACS of the prefrontal cortex Device: 80 Hz tACS of the bilateral somatosensory cortex Device: 80 Hz tACS of the prefrontal cortex Device: Sham stimulation of the bilateral somatosensory cortex Device: Sham stimulation of the prefrontal cortex Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Each participant will participate in 6 experimental conditions aimed at studying the effect of different tACS protocols on pain processing: (1) 10 Hz tACS of the bilateral somatosensory cortex, (2) 10 Hz tACS of the prefrontal cortex, (3) 80 Hz tACS of the bilateral somatosensory cortex, (4) 80 Hz tACS of the prefrontal cortex, (5) sham stimulation of the bilateral somatosensory cortex, and (6) sham stimulation of the prefrontal cortex. Each condition will be administered in an individual session. Sessions will be conducted in pseudo-randomized order and separated by at least 24 hours to avoid any carry-over effects of the stimulation. During each tACS administration, pain will be induced by means of an established tonic thermal stimulation paradigm lasting for several minutes (TSA-II; Medoc, Ramat Yishai, Israel) while pain ratings and autonomic responses will be recorded (Nickel et al., 2017a; Nickel et al., 2017b).
Masking: None (Open Label)
Masking Description: Neither participants nor the conducting investigator will be informed about the administered tACS protocol (10 Hz tACS, 80 Hz tACS or sham stimulation) (= double-blind study). Blinding of participants will be achieved by using tACS intensities which should not evoke perceivable stimulation side effects like skin or visual sensations. Blinding of participants will be controlled using post-hoc questionnaires. An unblinded research assistant who does not interact with the participants will be responsible for initiating and monitoring the appropriate tACS protocol and, thus, enable the blinding of the conducting investigator.
Primary Purpose: Basic Science
Official Title: Modulating Pain Using Transcranial Alternating Stimulation (tACS) in Healthy Human Subjects
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Transcranial alternating current stimulation (tACS) Device: 10 Hz tACS of the bilateral somatosensory cortex
10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

Device: 10 Hz tACS of the prefrontal cortex
10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.

Device: 80 Hz tACS of the bilateral somatosensory cortex
80 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

Device: 80 Hz tACS of the prefrontal cortex
80 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.

Device: Sham stimulation of the bilateral somatosensory cortex
10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

Device: Sham stimulation of the prefrontal cortex
10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber placed at electrode positions F3 and F4 according to the international 10-20 system.




Primary Outcome Measures :
  1. Changes in pain rating on visual analogue scale (VAS; 0: 'no pain' to 10: 'maximal tolerable pain') between sessions [ Time Frame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs. ]
    During thermal stimulation, participants will be instructed to continuously rate the currently perceived pain intensity using a finger-span device.

  2. Changes in skin conductance responses (µS) between sessions [ Time Frame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs. ]
    Skin conductance responses will be recorded using two electrodes attached to the index and middle finger of the left hand.

  3. Changes in heart rate (BPM, beats per minute) between sessions [ Time Frame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs. ]
    The electrocardiogram (ECG) will be recorded using two electrodes placed under the right clavicle and below the sternum, respectively.

  4. Changes in oscillatory brain activity before and after tACS application within each session [ Time Frame: Measured immediately before and after the tACS protocol in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs. ]
    5-minute resting state electroencephalogram (EEG) will be recorded with two electrodes placed at the same electrode positions used for the respective tACS protocol. Power of oscillatory brain activity will be quantified in the alpha (8-12 Hz) and gamma (30-100 Hz) bands.


Secondary Outcome Measures :
  1. Perception of tACS induced visual and skin sensations measured by numerical rating scale (NRS; 0: 'no sensation' to 10: 'very strong sensation') [ Time Frame: Measured immediately after the EEG measurement following each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs. ]
    The perception of visual and skin sensations induced by the tACS protocols will be assessed using a custom questionnaire.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • aged 18-65 years
  • Right-handedness
  • Written informed consent

Exclusion Criteria:

  • Pregnancy
  • Neurological or psychiatric diseases (e.g. epilepsy, stroke, depression, anxiety disorders)
  • Severe general illnesses (e.g. tumors, diabetes)
  • Skin diseases (e.g. dermatitis, psoriasis or eczema)
  • Current or recurrent pain
  • Regular intake of medication
  • Surgical procedures involving the head or spinal cord
  • Head trauma followed by impairment of consciousness
  • Past fainting spells or syncopes
  • Metal (except titanium) or electronic implants
  • Side-effects following previous electrical or magnetic stimulation
  • Side-effects following previous thermal stimulation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03805854


Contacts
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Contact: Markus Ploner, Prof. Dr. med. +49-89-4140-4608 markus.ploner@tum.de

Locations
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Germany
Department of Neurology, Klinikum rechts der Isar, Technische Universität München Recruiting
Munich, Bavaria, Germany, 81675
Contact: Markus Ploner, Prof. Dr. med.    +49-89-4140-4608    markus.ploner@tum.de   
Sponsors and Collaborators
Technische Universität München
German Research Foundation
Investigators
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Principal Investigator: Markus Ploner, Prof. Dr. med. Department of Neurology, Klinikum rechts der Isar, Technische Universität München

Publications:

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Responsible Party: Markus Ploner, Heisenberg Professor of Human Pain Research, Technische Universität München
ClinicalTrials.gov Identifier: NCT03805854     History of Changes
Other Study ID Numbers: 01/2019
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pseudonymized individual participant data sets will be made available at the OSF online repository [https://osf.io/] upon publication.
URL: https://osf.io/pnd6g/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Markus Ploner, Technische Universität München:
pain
tACS
alpha
gamma
neural oscillations
brain