Acute PainPhase 2NCT02432677
Evaluation of the Potentiating Effect of tDCS on Opioid Analgesia of Pain Threshold in Humans
A Phase 2 study testing Remifentanil and Active tDCS in people with Acute Pain, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Acute Pain
- What is being tested?
- Remifentanil and Active tDCS
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteBrazil
- Study dates
- Jul 2014to Apr 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male
- Healthy
- Without medication
- Sign the informed consent
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital de Clinicas e Porto Alegre (HCPA)
Porto Alegre, Rio Grande do Sul, 90035-003
Wolnei Caumo, 55 51 99813977, caumo@cpovo.net
Wolnei Caumo
About this study
Official title: Evaluation of the Potentiating Effect of Transcranial Direct Current Stimulation (tDCS) on Opioid Analgesia of Pain Threshold in Humans
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 .
Read the 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.
- Conditions
- Acute Pain
- Being tested
- Remifentanil, Active tDCS, Sham tDCS, Placebo
- Keywords
- tDCS, Opioid, Pain, Pain threshold
- Medical subject headings
- Acute Pain, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemifentanilDrug
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.
Active tDCSDevice
Also called transcranial direct current stimulation
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.
Sham tDCSDevice
Also called Sham - transcranial direct current stimulation
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.
PlaceboDrug
Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
| Study group | Role | What they receive |
|---|---|---|
| Remifentanil + Active tDCS | Experimental | * 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. Receives: Drug: Remifentanil; Device: Active tDCS |
| Placebo + Active tDCS | Other | * 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. Receives: Device: Active tDCS; Drug: Placebo |
| Remifentanil + Sham tDCS | Other | * 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. Receives: Drug: Remifentanil; Device: Sham tDCS |
| Placebo + Sham tDCS | Other | * 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. Receives: Device: Sham tDCS; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thresholds of pain to the cold pressor test (CPT)
Measured: 20min
Secondary outcomes (7)
Serum levels of BDNF
Measured: 20min
Intensity of electrical brain activity in the bi-spectral index (BIS)
Measured: 60min
Sedation level in the visual analogue scale (VAS)
Measured: 60min
Temperature of tolerance to the thermal stimulus (TTTS)
Measured: 20min
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.
Measured: 20min
Threshold of pain to the thermal stimulus (TT)
Measured: 20min
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.
Measured: 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2015 (estimated)
- Study startJul 2014
- Primary completionDec 2015 (estimated)
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute PainStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wolnei Caumo, MD, P.h.D, Principal investigator, Hospital de Clinicas de Porto Alegre - UFRGS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02432677
- Sponsor's protocol ID
- 14-0217
- Status last verified
- Apr 2015
- First submitted
- 6 Apr 2015
- Last updated
- 4 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29515438
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Potentiating Effect of Transcranial Direct Current Stimulation (tDCS) on Opioid Analgesia of Pain Threshold in Humans
- ClinicalTrials.gov ID
- NCT02432677
- Acronym / sponsor ID
- 14-0217
- Conditions
- Acute Pain
- Keywords
- tDCS, Opioid, Pain, Pain threshold
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Apr 2016 (estimated)
- First posted
- 4 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Remifentanil + Active tDCS | Experimental | Drug: Remifentanil, Device: Active tDCS* 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. |
| Placebo + Active tDCS | Other | Device: Active tDCS, Drug: Placebo* 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. |
| Remifentanil + Sham tDCS | Other | Drug: Remifentanil, Device: Sham tDCS* 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. |
| Placebo + Sham tDCS | Other | Device: Sham tDCS, Drug: Placebo* 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male
- Healthy
- Without medication
- Sign the informed consent
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemifentanilRemifentanil (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. | Drug | Remifentanil + Active tDCS, Remifentanil + Sham tDCS |
| Active tDCSAlso: transcranial direct current stimulationThe 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. | Device | Placebo + Active tDCS, Remifentanil + Active tDCS |
| Sham tDCSAlso: Sham - transcranial direct current stimulationThe 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. | Device | Placebo + Sham tDCS, Remifentanil + Sham tDCS |
| PlaceboSaline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests. | Drug | Placebo + Active tDCS, Placebo + Sham tDCS |
Primary outcome
Thresholds of pain to the cold pressor test (CPT)
Time frame: 20min
7 secondary outcomes
Serum levels of BDNF
Time frame: 20min
Intensity of electrical brain activity in the bi-spectral index (BIS)
Time frame: 60min
Sedation level in the visual analogue scale (VAS)
Time frame: 60min
Temperature of tolerance to the thermal stimulus (TTTS)
Time frame: 20min
Conditioned pain modulation (CPM)
Time frame: 20min
Threshold of pain to the thermal stimulus (TT)
Time frame: 20min
Hemodynamic changes of brain using fNIRSNear-infrared spectroscopy (NIRS)
Time frame: 60
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2015.
- Derived from this study: PubMed 29515438Braulio 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wolnei Caumo, MD, P.h.D principal investigator
Hospital de Clinicas de Porto Alegre - UFRGS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Remifentanil and Active tDCS in people with Acute Pain, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gilberto Braulio, MD (+555183008300, gbraulio@hcpa.ufrgs.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thresholds of pain to the cold pressor test (CPT) (time frame: 20min). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02432677, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2015.