Evaluation of the Potentiating Effect of tDCS on Opioid Analgesia of Pain Threshold in Humans

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Primary Purpose

Status

Unknown status

Phase

Phase 2

Locations

Brazil

Study Type

Interventional

Intervention

Remifentanil

Active tDCS

Sham tDCS

Placebo

About this trial

This is an interventional treatment trial for Acute Pain focused on measuring tDCS, Opioid, Pain, Pain threshold

Eligibility Criteria

18 Years - 40 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Male
Healthy
Without medication
Sign the informed consent

Exclusion Criteria:

Patients who did not understand the Portuguese
Acute or chronic pain conditions
Medical or psychiatric disorders
History of sleep disorders (apnea, hypersomnia, somnambulism…)
History of alcohol or substance abuse
Neurological disorder
Use of anti-inflammatory drugs, steroids and non-steroids, opioid and non-opioid analgesics, psychiatric medications, anticonvulsants, alpha and beta blockers
Traumatic brain injury
Neurosurgery
Metallic implant in the brain

Sites / Locations

Hospital de Clinicas e Porto Alegre (HCPA)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Other

Arm Label

Remifentanil + Active tDCS

Placebo + Active tDCS

Remifentanil + Sham tDCS

Placebo + Sham tDCS

Arm Description

tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Outcomes

Primary Outcome Measures

Thresholds of pain to the cold pressor test (CPT)

Secondary Outcome Measures

Serum levels of BDNF

Intensity of electrical brain activity in the bi-spectral index (BIS)

Sedation level in the visual analogue scale (VAS)

Temperature of tolerance to the thermal stimulus (TTTS)

Conditioned pain modulation (CPM)

A nociceptive tonic conditioning stimulus - immersion of the non-dominant hand in cold water (0°C for 1 minute) - will be applied concomitant to the progressive thermal stimulus in the dominant forearm as applied in the QST pattern until it reaches the 6/10 pain temperature previously determined by the participant.

Threshold of pain to the thermal stimulus (TT)

Hemodynamic changes of brain using fNIRSNear-infrared spectroscopy (NIRS)

The vascular response will be assessed using functional near infrared spectroscopy (fNIRS). Emerging technique that allows the functional mapping of the brain, with a better understanding of the neuro-vascular coupling, the neurophysiological fluctuations and cerebral hemodynamics.

Full Information

NCT ID

NCT02432677

First Posted

April 6, 2015

Last Updated

April 28, 2015

Sponsor

Hospital de Clinicas de Porto Alegre

1. Study Identification

Unique Protocol Identification Number

NCT02432677

Brief Title

Evaluation of the Potentiating Effect of tDCS on Opioid Analgesia of Pain Threshold in Humans

Official Title

Evaluation of the Potentiating Effect of Transcranial Direct Current Stimulation (tDCS) on Opioid Analgesia of Pain Threshold in Humans

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Unknown status

Study Start Date

July 2014 (undefined)

Primary Completion Date

December 2015 (Anticipated)

Study Completion Date

April 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospital de Clinicas de Porto Alegre

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this study is to evaluate the potential additive effect of tDCS compared to placebo-sham in opioid analgesia on pain thresholds in nociceptive experimental model in healthy volunteers .

Detailed Description

Pain is a prevalent symptom in medicine and the role of various opioids is valuable in the treatment of moderate to severe pain. Several technologies of brain stimulation , including transcranial direct current stimulation ( tDCS) are emerging as therapeutic options for many pain conditions. The effect of tDCS was demonstrated in sensory perception , decreasing the threshold for acute pain in healthy volunteers and in various chronic pain conditions . There is evidence about the use of tDCS with the participation through many mechanisms in cortical modulation , including the regulation of neurotransmitters, including opioids. In the context of neurostimulation, opioidergic system and cortical pain modulation, emerge the hypothesis of a possible potentiating effect of tDCS on clinical application of opioid analgesia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Pain

Keywords

tDCS, Opioid, Pain, Pain threshold

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Remifentanil + Active tDCS

Arm Type

Experimental

Arm Description

tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Arm Title

Placebo + Active tDCS

Arm Type

Other

Arm Description

tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Arm Title

Remifentanil + Sham tDCS

Arm Type

Other

Arm Description

Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Arm Title

Placebo + Sham tDCS

Arm Type

Other

Arm Description

Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Intervention Type

Drug

Intervention Name(s)

Remifentanil

Intervention Description

Remifentanil (IV infusion): 0,06mcg.kg.min. The infusion starts 10min before tDCSThe infusion will be stopped in the event of: a decrease in respiratory rate below 7 breaths / min, a peripheral oxygen saturation below 85%, a lower heart rate of 40 beats per minute, a lower mean arterial pressure of 60 mmHg, sedation causing inadequate management switch stimuli tests and occurrence of vomiting.

Intervention Type

Device

Intervention Name(s)

Active tDCS

Other Intervention Name(s)

transcranial direct current stimulation

Intervention Description

The stimulation will be administered with a pair of surface electrodes, sponge coated, soaked in saline. A battery-powered constant current stimulator will be used for this purpose (tDCS device). The stimulation is performed by placing the anodal electrode in the primary motor cortex (M1) and the cathodal one in the contralateral supraorbital area and it will use a 2 mA (milliampere) current.

Intervention Type

Device

Intervention Name(s)

Sham tDCS

Other Intervention Name(s)

Sham - transcranial direct current stimulation

Intervention Description

The sham tDCS consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.

Primary Outcome Measure Information:

Title

Thresholds of pain to the cold pressor test (CPT)

Time Frame

20min

Secondary Outcome Measure Information:

Title

Serum levels of BDNF

Time Frame

20min

Title

Intensity of electrical brain activity in the bi-spectral index (BIS)

Time Frame

60min

Title

Sedation level in the visual analogue scale (VAS)

Time Frame

60min

Title

Temperature of tolerance to the thermal stimulus (TTTS)

Time Frame

20min

Title

Conditioned pain modulation (CPM)

Description

A nociceptive tonic conditioning stimulus - immersion of the non-dominant hand in cold water (0°C for 1 minute) - will be applied concomitant to the progressive thermal stimulus in the dominant forearm as applied in the QST pattern until it reaches the 6/10 pain temperature previously determined by the participant.

Time Frame

20min

Title

Threshold of pain to the thermal stimulus (TT)

Time Frame

20min

Title

Hemodynamic changes of brain using fNIRSNear-infrared spectroscopy (NIRS)

Description

The vascular response will be assessed using functional near infrared spectroscopy (fNIRS). Emerging technique that allows the functional mapping of the brain, with a better understanding of the neuro-vascular coupling, the neurophysiological fluctuations and cerebral hemodynamics.

Time Frame

60

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male Healthy Without medication Sign the informed consent Exclusion Criteria: Patients who did not understand the Portuguese Acute or chronic pain conditions Medical or psychiatric disorders History of sleep disorders (apnea, hypersomnia, somnambulism…) History of alcohol or substance abuse Neurological disorder Use of anti-inflammatory drugs, steroids and non-steroids, opioid and non-opioid analgesics, psychiatric medications, anticonvulsants, alpha and beta blockers Traumatic brain injury Neurosurgery Metallic implant in the brain

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gilberto Braulio, MD

Phone

+555183008300

Email

gbraulio@hcpa.ufrgs.br

First Name & Middle Initial & Last Name or Official Title & Degree

Wolnei Caumo, MD, P.h.D

Phone

+55 51 99813977

Email

caumo@cpovo.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wolnei Caumo, MD, P.h.D

Organizational Affiliation

Hospital de Clinicas de Porto Alegre - UFRGS

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital de Clinicas e Porto Alegre (HCPA)

City

Porto Alegre

State/Province

Rio Grande do Sul

ZIP/Postal Code

90035-003

Country

Brazil

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wolnei Caumo

Phone

55 51 99813977

Email

caumo@cpovo.net

First Name & Middle Initial & Last Name & Degree

Wolnei Caumo

12. IPD Sharing Statement

Citations:

PubMed Identifier

29515438

Citation

Braulio G, Passos SC, Leite F, Schwertner A, Stefani LC, Palmer ACS, Torres ILS, Fregni F, Caumo W. Effects of Transcranial Direct Current Stimulation Block Remifentanil-Induced Hyperalgesia: A Randomized, Double-Blind Clinical Trial. Front Pharmacol. 2018 Feb 19;9:94. doi: 10.3389/fphar.2018.00094. eCollection 2018.

Results Reference

derived

Acute Pain

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial