Neurophysiological Effects on tPCS and tDCS on Healthy Subjects and on Patients With Chronic Visceral Pain

This study investigates comparing the effects of transcranial Pulsed Current Stimulation and transcranial Direct Current Stimulation (tDCS) (Soterix ©) and their combination on neurophysiological outcomes on healthy subjects as well as on the clinical population for chronic visceral pain. The study also aims to evaluate the effects of these techniques on pain thresholds in healthy subjects as well as for chronic visceral pain patients.

Study Overview

• Status: Completed
• Conditions: Pelvic Pain; Pancreatitis; Visceral Pain
• Intervention / Treatment: Device: Active tPCS; Device: Active tDCS; Device: Sham tDCS; Device: Sham tPCS

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Spaulding Rehabilitation Network Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

PART 1: 48 healthy subjects will be selected to take part in this study. All healthy subjects will need to meet all of the following inclusion criteria and none of the following exclusion criteria:

Inclusion criteria:

• Provide informed consent to participate in the study
• Age 18 - 60 years

Exclusion criteria:

• History of alcohol or substance abuse within the last 6 months as self-reported
• Severe depression (with a score of >30 in the Beck Depression Inventory)*
• History of seizures during the last two years or diagnosis of epilepsy
• History of neurological or psychiatric illness
• Unstable medical conditions such as uncontrolled diabetes mellitus, uncompensated cardiac pathology, heart failure, kidney insufficiency or chronic obstructive pulmonary disease, acute thrombosis
• History of head injury resulting in more than a momentary loss of consciousness during the last two years
• History of unexplained fainting spells or loss of consciousness as self-reported during the last two years
• Contraindication to tPCS or tDCS
• Metallic brain implants
• Implanted brain electronic medical devices
• Pregnancy
• Use of neuropsychotropic drugs within the past two weeks as self reported

Part 2: 18 patients with Chronic Visceral Pain will take part in this experiment. All subjects must meet the following criteria:

Inclusion criteria:

• Provide informed consent to participate in the study
• Age 18 - 60 years
• Abdominal or pelvic pain for ≥ 3 days per week for at least 3 months (average VAS scale score of 4/10 or greater at time of enrollment) as self reported
• Diagnosis of chronic visceral pain (e.g. Chronic Pancreatitis or Chronic Pelvic Pain) as confirmed by medical records or a letter from their physician
• If taking pain medications, stable doses are required for at two weeks prior to initiation of the study

Exclusion criteria:

• History of alcohol or substance abuse within the last 6 months as self-reported
• Severe depression (with a score of >30 in the Beck Depression Inventory)*
• Epilepsy
• Unstable medical conditions such as uncontrolled diabetes mellitus, uncompensated cardiac pathology, heart failure, kidney insufficiency or chronic obstructive pulmonary disease, acute thrombosis
• History of head injury resulting in more than a momentary loss of consciousness during the last two years
• History of unexplained fainting spells or loss of consciousness as self-reported during the last two years
• Contraindication to tPCS or tDCS
• Metallic brain implants
• Implanted brain electronic medical devices
• Pregnancy or trying to become pregnant during the next month
• Use of carbamazepine oxcarbazepine, phenytoin, pramipexole (Mirapex), or cavergoline (Dostinex) within the past 6 months as self-reported

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1:Active tPCS, Active tDCS; 12 out of the 48 total health subjects will receive active tPCS and active tDCS. This will be done for 20 minutes simultaneously.	Device: Active tPCS; A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will be used with a peri-aurical ear-clip electrode montage for 20 minutes.; Device: Active tDCS; A current intensity of 2.0 mA will be used for 20 minutes. The electrodes that will be used will be standard sponge electrodes. The anode will be placed over left motor cortex. The cathode electrode will be placed over the contralateral supraorbitofrontal area.
Experimental: Part 1: Active tPCS, Sham tDCS; 12 out of the 48 total health subjects will receive active tPCS and sham tDCS. This will be done for 20 minutes simultaneously.	Device: Active tPCS; A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will be used with a peri-aurical ear-clip electrode montage for 20 minutes.; Device: Sham tDCS; Sham tDCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2.0 mA will still be used (but turned off after 30 seconds using ramping). The electrodes that will be used will be same, standard sponge electrodes. The anode will be placed over the left motor cortex The cathode electrode will be placed over the contralateral supraorbitofrontal area.
Experimental: Part 1:Sham tPCS, Active tDCS; 12 out of the 48 total health subjects will receive sham tPCS and active tDCS. This will be done for 20 minutes simultaneously.	Device: Active tDCS; A current intensity of 2.0 mA will be used for 20 minutes. The electrodes that will be used will be standard sponge electrodes. The anode will be placed over left motor cortex. The cathode electrode will be placed over the contralateral supraorbitofrontal area.; Device: Sham tPCS; Sham tPCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will still be used (only this will be turned off after 30 seconds using ramping) with a peri-aurical ear-clip electrode montage.
Sham Comparator: Part 1: Sham tDCS, Sham tDCS; 12 out of the 48 total health subjects will receive sham tPCS and sham tDCS. This will be done for 20 minutes simultaneously.	Device: Sham tDCS; Sham tDCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2.0 mA will still be used (but turned off after 30 seconds using ramping). The electrodes that will be used will be same, standard sponge electrodes. The anode will be placed over the left motor cortex The cathode electrode will be placed over the contralateral supraorbitofrontal area.; Device: Sham tPCS; Sham tPCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will still be used (only this will be turned off after 30 seconds using ramping) with a peri-aurical ear-clip electrode montage.
Experimental: Part 2: Active tPCS/Active tDCS; Part 2 will run as a four-period crossover design, where all chronic visceral pain subjects (18 total) will be receiving all (4) possible combinations of tDCS and tPCS interventions (active or sham) at the end of the experiment in a random, consecutive way. This represents the combination of receiving active tPCS and active tDCS (1/4 combinations all subjects will receive).	Device: Active tPCS; A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will be used with a peri-aurical ear-clip electrode montage for 20 minutes.; Device: Active tDCS; A current intensity of 2.0 mA will be used for 20 minutes. The electrodes that will be used will be standard sponge electrodes. The anode will be placed over left motor cortex. The cathode electrode will be placed over the contralateral supraorbitofrontal area.
Experimental: Part 2: Active tPCS/Sham tDCS; Part 2 will run as a four-period crossover design, where all chronic visceral pain subjects (18 total) will be receiving all (4) possible combinations of tDCS and tPCS interventions (active or sham) at the end of the experiment in a random, consecutive way. This represents the combination of receiving active tPCS and sham tDCS (1/4 combinations all subjects will receive).	Device: Active tPCS; A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will be used with a peri-aurical ear-clip electrode montage for 20 minutes.; Device: Sham tDCS; Sham tDCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2.0 mA will still be used (but turned off after 30 seconds using ramping). The electrodes that will be used will be same, standard sponge electrodes. The anode will be placed over the left motor cortex The cathode electrode will be placed over the contralateral supraorbitofrontal area.
Experimental: Part 2: Sham tPCS/Active tDCS; Part 2 will run as a four-period crossover design, where all chronic visceral pain subjects (18 total) will be receiving all (4) possible combinations of tDCS and tPCS interventions (active or sham) at the end of the experiment in a random, consecutive way. This represents the combination of receiving sham tPCS and active tDCS (1/4 combinations all subjects will receive).	Device: Active tDCS; A current intensity of 2.0 mA will be used for 20 minutes. The electrodes that will be used will be standard sponge electrodes. The anode will be placed over left motor cortex. The cathode electrode will be placed over the contralateral supraorbitofrontal area.; Device: Sham tPCS; Sham tPCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will still be used (only this will be turned off after 30 seconds using ramping) with a peri-aurical ear-clip electrode montage.
Sham Comparator: 2: Sham tPCS/Sham tDCS; Part 2 will run as a four-period crossover design, where all chronic visceral pain subjects (18 total) will be receiving all (4) possible combinations of tDCS and tPCS interventions (active or sham) at the end of the experiment in a random, consecutive way. This represents the combination of receiving sham tPCS and sham tDCS (1/4 combinations all subjects will receive).	Device: Sham tDCS; Sham tDCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2.0 mA will still be used (but turned off after 30 seconds using ramping). The electrodes that will be used will be same, standard sponge electrodes. The anode will be placed over the left motor cortex The cathode electrode will be placed over the contralateral supraorbitofrontal area.; Device: Sham tPCS; Sham tPCS stimulation will consist of applying the same parameters as for active, but the corresponding device will be turned off after 30 seconds, as to simulate the initial sensation of the active current. A current intensity of 2mA and a stimulation frequency range of 6-10 Hz will still be used (only this will be turned off after 30 seconds using ramping) with a peri-aurical ear-clip electrode montage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signal Coherence and EEG power as measured Quantitative Electroencephalographic Analysis (qEEG):	The EEG test is performed to measure the electrical activity in the brain and to examine the dynamic changes.	For the healthy subjects during their 1-time study visit; For visceral pain patients, it will be measured over the course of about 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure Values as measured by Pain Pressure Test (PPT) for Conditioned Pain Modulation (CPM)	These procedures incorporate a conditioning stimulus (a noxious stimulus that evokes Descending Noxious Inhibitory Control (DNIC) activation) and a test stimulus (a noxious stimulus used to evaluate the analgesic response to the conditioning stimulus- this will be the PPT as determined by an algometer (JTECH medical)). This study will evaluate CPM in healthy subjects as well as in patients with chronic visceral pain using pressure as the test stimulus, and cold water as the conditioning stimulus.	For the healthy subjects during their 1-time study visit; For visceral pain subjects, it will be measured over the course of about 3 weeks
Sensitivity of Filaments as measured by Von Frey assessment	This assessment will be performed before and after every intervention on a patient with pain. Mechanical perception and pain threshold will be tested on the painful region and on other non-painful area Von Frey monofilaments (0.4 g to 50 g) (these are fine filaments that can test a subject's perception threshold when they are applied to the body surface). Monofilament application will be applied to the painful region and a non painful region on the same side of the body (i. e. left or right). The hairs will be applied until subject perceives the stimulus (perception threshold) and describes it as painful (pain threshold). The threshold will be taken as the lowest force that causes pain perception in the affected and contralateral mirror healthy site.	Only done for visceral pain subjects; it will be measured over the course of about 3 weeks.
Pain score as measured by Visual Analogue Scale (VAS) for Pain:	The VAS is a self-reporting test asking subjects to self-measure their pain on a visual scale from zero to ten (i.e., none to unbearable). This will help us monitor changes in subjects' pain levels when they come in for sessions.	Only done for visceral pain subjects; it will be measured over the course of about 3 weeks.
Pain levels and medication intake as measured Pain/Medication Diary	To monitor pain levels, as well as safety, patients with chronic visceral pain will keep a diary listing their daily medications and pain levels when not at the laboratory.	Only done for visceral pain subjects; it will be measured over the course of about 3 weeks
Mood scores as measured Visual Analog Mood Scale (VAMS)	This is a self-reporting assessment in which subjects rate their own emotions, including anxiety, depression, stress, and sleepiness along a 100mm line.	Only done for visceral pain subjects; it will be measured over the course of about 3 weeks
Depression level as measured Beck Depression Inventory (BDI)	A 21-item, multiple-choice questionnaire will be administered at the beginning of the study to all subjects to assess the presence and degree of depression in adults, as studies in chronic pain have found that depression can modulate pain perception.	Done for both healthy and visceral pain subjects during screening (first study visit)
Effectiveness of blinding as measured by the tPCS and tDCS Blinding Questionnaire	After the stimulation session, subjects will complete a questionnaire to determine if the blinding methods were effective. A 30s sham montage is used,which is consistent with other trials, keeping the device on the subject for the duration of the session.	For the healthy subjects during their 1-time study visit; For visceral pain subjects, it will be measured over the course of about 3 weeks
Side-effects from stimulation as measured by the tDCS and tPCS Side Effects Questionnaire	At the end of each stimulation session, subjects will complete a questionnaire to evaluate potential side effects of stimulation (headache, neck pain, mood alterations, and seizures) on a 5-point scale. Subjects will be asked whether they have experienced any side effects in open-ended questions. They will also be specifically asked about headache, neck pain, scalp pain, scalp burns, tingling, skin redness, sleepiness, trouble concentrating, and acute mood change. If any side effects are reported, the degree of relatedness to the intervention will be assessed.This assessment identifies adverse effects using open-ended questions.	For the healthy subjects during their 1-time study visit; For visceral pain subjects, it will be measured over the course of about 3 weeks

Collaborators and Investigators

• Sponsor: Spaulding Rehabilitation Hospital
• Investigators: Principal Investigator: Felipe Fregni, MD, PhD, MPH, Spaulding Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: July 9, 2015
• First Submitted That Met QC Criteria: July 9, 2015
• First Posted (Estimate): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: tDCS; healthy subjects; neuromodulation; pancreatitis; visceral pain; non-invasive brain stimulation; pelvic pain; TPCS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pain; Neurologic Manifestations; Pancreatic Diseases; Nociceptive Pain; Pancreatitis; Pelvic Pain; Visceral Pain
• Other Study ID Numbers: 2015P000365

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No