Chronic PainNCT05099406
Home-based Transcranial Stimulation in the Treatment of Patients With Refractory Chronic Pain
A study testing Transcranial electrical stimulation in people with Chronic Pain, run by University of Santiago de Compostela at 1 site in Spain.
Trial summary
Refractory chronic pain represents a serious and limiting health condition which does not respond to standard pharmacological therapy. Thus, it emerges the necessity of new techniques to treat these group of diseases, such as the transcranial electrical stimulation (tES). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Pain
- What is being tested?
- Transcranial electrical stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2022to 1 May 2023
- Phase
- Interventional
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Suffering a chronic pain condition of non-cancer nature. Those patients who report chronic pain even after overcoming an oncological process are suitable to participate, but only if they have received the definitive medical discharge and have been free from radiotherapy/chemotherapy for at least twelve months.
- Adult subjects (18-65 years old).
- Subjects able to provide informed consent to participate in the study and to self-report pain.
- Existing chronic pain which reaches an intensity of at least 4 on a 0-10 Numeric Rating Scale (NRS) on average over the past 3 months prior to enrolment.
- Pain intensity of at least 5 on a 0-10 NRS over the week prior to enrolment.
- Diagnosis of pharmaco-resistance to analgesic drugs across the WHO ladder.
- Pharmacological regimen have kept stable for at least two months previous to the enrolment, and it must not suffer modifications during the whole research period.
Who cannot join
- Chronic pain derived from current cancer disease.
- Pregnant women or women in fertile age not having efficacious contraception during the whole period of the study.
- History of alcohol or drug abuse within the past 6 months as self-reported.
- Suffering from unstable medical conditions (e.g., uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease).
- Intracranial ferromagnetic devices or implanted stimulator (basal ganglia stimulator, vagus nerve stimulation).
- Antecedents of, or active epilepsy.
- History of neurosurgery, psychiatric diseases other than anxiety or depression, traumatic brain injury with loss of consciousness, and/or cortical lesions.
Trial locations and contacts
1 site in 1 country.
J. Antonio Vázquez Millán contact
Spain1 site, 1 recruiting
- Recruiting
University of Santiago de Compostela
Santiago de Compostela, A Coruña, 15701
María Teresa Carrillo de la Peña, PhD, +34 625 76 32 25, mteresa.carrillo@usc.es
María Teresa Carrillo de la Peña, PhD, University teacher
About this study
Official title: Brain and Pain (BaP): Understanding the Central Mechanisms of Pain to Improve Management of Patients With Refractory Chronic Pain
Refractory chronic pain represents a serious and limiting health condition which does not respond to standard pharmacological therapy. Thus, it emerges the necessity of new techniques to treat these group of diseases, such as the transcranial electrical stimulation (tES). This procedure induces a low-intensity electrical current through the scalp to modify the excitability of brain cells, thus facilitating changes in neural networks which may be dysfunctional in some chronic pain patients.
The main objective of this research is to test the efficacy of two tES techniques, differentiated by applying direct or alternant electrical current, to reduce the pain intensity and to increase pain thresholds of these patients. Besides, intervention is implemented at home for patients themselves thanks to a portable and convenient stimulator device, after one training session provided by technicians. Researches can supervise the compliance of the treatment remotely, as the stimulator has a permanent connection with their computers. A home-based approach means a more comfortable and accessible treatment alternative for patients, since they do not have to attend to clinics everyday to receive the stimulation; the advantages become even more relevant in the pandemic context, since the risk of being infected is radically minimized.
Despite the main purpose is to test the efficacy of tES to improve the pain suffered by patients, many other areas are considered as secondary end points for being intrinsically linked or affected by the disease, such as the interference in daily tasks provoked by pain, mood disorders (depression/anxiety), fatigue, life quality, physical functioning and sleep quality; these last two variables are measured with actigraph wristwatches, apart from specific questionnaires. Lastly, endogenous modulatory pain mechanisms are examined through sensory tests, namely Conditioned Pain Modulation and Temporal Summation of pain.
Read the detailed description
This work aims to provide answers to the refractory chronic pain challenge. Pain is defined as refractory when multiple evidence-based biomedical therapies have failed to reach treatment goals that may include adequate pain reduction and/or improvement in daily functioning, even after appropriately assessing and addressing those psychosocial factors that could influence pain outcomes. In this sense, on the one hand, the study focus on detecting central biomarkers of pain modulation and processing which will contribute to improving knowledge of the mechanisms of pain chronification and the diagnosis procedure. On the other hand, given the low efficacy of pharmacological or non-pharmacological therapies for the patients studied, the efficacy of new therapeutic alternatives (tES) is explored. In short, the project will allow the transfer of knowledge to clinical practice in several aspects, such as diagnosis or treatment.
Therefore, the research aims to test the role of defective central pain modulation/processing as explanatory mechanisms for chronic pain. A second main objective is to test the efficacy of transcranial electric stimulation (tES) to modify dysfunction of central mechanism of pain, and to improve symptoms and quality of life in refractory chronic pain patients.
To achieve this, the investigators will select valid and reliable instruments to assess pain and comorbid symptoms in chronic pain patients and the most sensitive outcome measures to assess tES treatment efficacy. Sensory testing paradigms, namely Conditioned Pain Modulation, Temporal Summation of Second Pain and pain-related evoked potentials using electroencephalographic recordings, will act as biomarkers which are proposed to correlate with the severity of the chronic pain disease or some of their symptoms, and also as predictors of the treatment outcome.
Total sample includes 120 patients with refractory pharmaco-resistant pain, attended at the Pain Units of two Public Galician Hospitals (36 male, 84 female).
The study is expected to contribute to detection and preventive measures of future pain, and diagnosis of chronic pain disorders, improving prognosis and development of feasible patient-centered interventions, providing new directions for future research on pain.
- Conditions
- Chronic Pain
- Being tested
- Transcranial electrical stimulation
- Keywords
- Transcranial electrical stimulation, Fibromyalgia, Arthritis, Arthrosis, Low back pain, Migraine headaches, Anxiety disorders, Depression, Chronic fatigue, Sleep disorders, Pain assessment, EEG
- Medical subject headings
- Chronic Pain, Fibromyalgia, Arthritis, Osteoarthritis, Low Back Pain, Migraine Disorders, Anxiety Disorders, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial electrical stimulationDevice
Also called Transcranial direct current stimulation, Transcranial alternant current stimulation
By applying a low current over the cortex through the scalp, this technique can excite or inhibit the neural activity, thus modulating brain processes like pain perception and inducing relatively sustained changes in cortical excitability and neuroplasticity.
Home-based transcranial electrical stimulation device consists of a custom headgear with fixed electrode sites and built-in cabling made for a simplistic setup for tDCS/tACS stimulation. Systems are equipped with strict dose control feature that provide reliable control over the intensity and timing of stimulation, turning these devices into a feasible and safe clinical alternative. The equipment is specifically designed for easy and simplistic self-setup and allows the researchers to remotely check the position of electrodes and also monitor the stimulation session.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial direct current stimulation (tDCS) | Active comparator | Fifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Current intensity of 2mA is applied during 20 minutes at the left M1, with anodal electrode placed in C3 and cathodal in FP2, following the International 10-20 EEG System. Ramp-up and ramp-down comprises 15 seconds at the beginning and end of the stimulation period. Receives: Device: Transcranial electrical stimulation |
| Transcranial alternant current stimulation (tACS) | Active comparator | Fifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Two electrodes will be placed at F3 and F4 and connected together for 10-Hz tACS (or the frequency which shows best sensitivity or specificity), and one electrode at Pz will be the return electrode. This setting is used to stimulate the somatosensory cortical region. Stimulation will last for 20 minutes, with a ramp-up and ramp-down of 15 seconds at the beginning and end of the session. Receives: Device: Transcranial electrical stimulation |
| Sham stimulation | Placebo comparator | The electrode montage will be either the tDCS (for half of the participants) or the tACS montage (for the other half), and we will just apply the current at the ramps terms, but no current in the interval between the ramps which practically comprises the whole session. As for the two other group, fifteen sham stimulation sessions will be daily scheduled in a non-interrupted period of two weeks. Receives: Device: Transcranial electrical stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Self-reported pain intensity
Participants must evaluate the intensity of their pain using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the worse the pain is.
Measured: Pre-treatment measure is the average of pain intensity of fifteen days previous to treatment; whereas the post-treatment measure is the average of fifteen days after treatment have finished
Secondary outcomes (14)
Global severity of chronic pain syndrome
Composed index about the gravity of the chronic pain condition, taking into account several parameters as social and professional limitations due to pain, frequency and intensity of pain crisis, among others. The severity of chronic pain syndrome is assessed with global and subscales scores of Multidimensional Pain Inventory (MPI). Higher scores are indicative of worse health condition.
Measured: Participants will complete MPI one or two days before the treatment onset, and one or two days after treatment ending.
Pressure pain threshold
Pressure pain threshold is defined as the minimum force necessary to induce pain in the participant, measured using a manual algometer and operationalized in kPa.
Measured: Pressure pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.
Heat pain threshold
Heat pain threshold is stablished as the temperature, measured in degrees Celsius, at which participant starts to feel pain, using a thermal stimulator.
Measured: Heat pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.
Interference in daily living caused by pain
Subscales of Multidimensional Pain Inventory (MPI) are used to evaluate whether patients usually leave undone or are not capable to do some daily activities and tasks due to the pain they suffer from. The test consists of a numerical rating scale of seven points (0-6), so that the higher the score is, the more pronounced is the interference due to pain.
Measured: Pain interference will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.
Life quality
General health status considering physical, emotional and social functionality, as well as physical and mental health. Life quality is measured using the Short Form-36 Health Survey (SF-36). Higher scores are indicative of better health condition.
Measured: Life quality will be assessed one or two days before the treatment onset and one or two days after treatment ending.
Physical condition and functioning
Involvement and time-spent in physical activities or exercises.
Measured: Estimations about daily energy expenditure, based on sedentary and activity bouts are recorded with wristband actigraphs which participants must wear during the whole research period.
Sleep quality and disturbances
Sleep habits of participants and the degree in which they perceive that sleep as restorative. Sleep quality is measured using the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Higher scores are indicative of poorer sleep quality.
Measured: Participants will complete PQSI at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending.
Sleep quality and disturbances
Sleep habits of participants, as total sleep time. This sleep parameter is measured using the data recorded for wristband actigraphs which participants must wear during the whole research period.
Measured: Wristband actigraph are given to patients fifteen days before the treatment onset, so sleep habits are monitorized since that moment, until fifteen days after treatment have finished
Pain unpleasantness
Affective component of pain, which refers to the discomfort or distress which pain provokes in patients. Participants must evaluate the discomfort produced by pain using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the more stressful the pain is.
Measured: Pre-treatment measure is the average of pain unpleasantness obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished
Mood disorders
Depressive and anxiety symptomatology which can concur with chronic pain conditions. Mood alterations are measured using the Hospital Anxiety and Depression Scale (HADS). Higher scores are indicative of a worse mood state.
Measured: Participants will complete HADS at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending.
Anxiety
General anxiety level are evaluated with a daily frequency using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the higher the anxiety level is.
Measured: Pre-treatment measure is the average of anxiety levels obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished
Fatigue
Tiredness which may result in difficulties to perform physical or psychological tasks. Fatigue and its consequences are measured using the Modified Impact Fatigue Scale (MFIS). Numerical Rating Scales of eleven points (0-10) are also used to assess daily fatigue levels. In both cases, higher scores are indicative of a greater fatigue.
Measured: Fatigue is registered with a daily frequency since the fifteen days before the treatment onset, until fifteen days after treatment ending. Participants will complete the MFIS at two time-points, this is, one or two days before and after treatment.
Caregiver burden
Stress levels which are subjected the caregivers of chronic pain patients are evaluated through the Zarit Burden Interview (ZBI) to assess if tES treatment means a reduction in burden derived from caring tasks. Higher scores are indicative of a more pronounced caregiver burden.
Measured: Caregivers are invited to a face-to-face interview with researchers one or two days before the treatment onset and one or two days after treatment ending.
Global satisfaction with treatment and self-perceived improvement
Patients are asked to rate their satisfaction with the tES treatment and whether they believe it has helped to improve their health status, using an ad-hoc designed questionnaire.
Measured: Participants will evaluate their satisfaction with treatment a few days after it had finished.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2021
- Study start1 Jan 2022 (estimated)
- Primary completion1 May 2023 (estimated)
- Study completion1 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned to one of three treatment groups (40% active tDCS; 40% Active tACS; 20% Sham). Patients receiving sham stimulation will act as the control group.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Santiago de Compostela
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Innovation, Spain, Health Research Institute of Santiago de Compostela - IDIS (Recruitment support), Fundación Biomédica Galicia Sur (Recruitment support)
- Responsible party
- Principal investigator, María Teresa Carrillo de la Peña, University of Santiago de Compostela
- Investigators
- María Teresa Carrillo de la Peña, Principal investigator, University of Santiago de Compostela
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05099406
- Sponsor's protocol ID
- 2019-PN133
- Other IDs
- 2021-000804-39
- Status last verified
- Oct 2021
- First submitted
- 30 Aug 2021
- Last updated
- 29 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Ahn S, Prim JH, Alexander ML, McCulloch KL, Frohlich F. Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study. J Pain. 2019 Mar;20(3):277.e1-277.e11. doi: 10.1016/j.jpain.2018.09.004. Epub 2018 Sep 27.
PubMed 30268803Antal A, Alekseichuk I, Bikson M, Brockmoller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Floel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19.
PubMed 28709880Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain. 2010 Jun;149(3):573-581. doi: 10.1016/j.pain.2010.04.003. Epub 2010 Apr 24.
PubMed 20418016Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-333. doi: 10.1016/j.ejpain.2005.06.009. Epub 2005 Aug 10.
PubMed 16095934Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013 Jul;14(7):502-11. doi: 10.1038/nrn3516. Epub 2013 May 30.
PubMed 23719569Choe MK, Lim M, Kim JS, Lee DS, Chung CK. Disrupted Resting State Network of Fibromyalgia in Theta frequency. Sci Rep. 2018 Feb 1;8(1):2064. doi: 10.1038/s41598-017-18999-z.
PubMed 29391478Davis KD, Flor H, Greely HT, Iannetti GD, Mackey S, Ploner M, Pustilnik A, Tracey I, Treede RD, Wager TD. Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations. Nat Rev Neurol. 2017 Oct;13(10):624-638. doi: 10.1038/nrneurol.2017.122. Epub 2017 Sep 8.
PubMed 28884750De Keyser R, van den Broeke EN, Courtin A, Dufour A, Mouraux A. Event-related brain potentials elicited by high-speed cooling of the skin: A robust and non-painful method to assess the spinothalamic system in humans. Clin Neurophysiol. 2018 May;129(5):1011-1019. doi: 10.1016/j.clinph.2018.02.123. Epub 2018 Mar 8.
PubMed 29567583de Tommaso M, Ricci K, Libro G, Vecchio E, Delussi M, Montemurno A, Lopalco G, Iannone F. Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials. Pain Res Treat. 2017;2017:9747148. doi: 10.1155/2017/9747148. Epub 2017 Sep 28.
PubMed 29093972Duenas M, Salazar A, Ojeda B, Fernandez-Palacin F, Mico JA, Torres LM, Failde I. A nationwide study of chronic pain prevalence in the general spanish population: identifying clinical subgroups through cluster analysis. Pain Med. 2015 Apr;16(4):811-22. doi: 10.1111/pme.12640. Epub 2014 Dec 19.
PubMed 25530229Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J; IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005 Jan;113(1-2):9-19. doi: 10.1016/j.pain.2004.09.012. No abstract available.
PubMed 15621359Fallon N, Chiu Y, Nurmikko T, Stancak A. Altered theta oscillations in resting EEG of fibromyalgia syndrome patients. Eur J Pain. 2018 Jan;22(1):49-57. doi: 10.1002/ejp.1076. Epub 2017 Jul 31.
PubMed 28758313Fernandes C, Pidal-Miranda M, Samartin-Veiga N, Carrillo-de-la-Pena MT. Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity. Pain. 2019 Dec;160(12):2679-2690. doi: 10.1097/j.pain.0000000000001664.
PubMed 31365469Frohlich F, Sellers KK, Cordle AL. Targeting the neurophysiology of cognitive systems with transcranial alternating current stimulation. Expert Rev Neurother. 2015 Feb;15(2):145-67. doi: 10.1586/14737175.2015.992782. Epub 2014 Dec 30.
PubMed 25547149Gonzalez-Villar AJ, Arias M, Carrillo-de-la-Pena MT. Brain Electrical Activity Associated With Visual Attention and Reactive Motor Inhibition in Patients With Fibromyalgia. Psychosom Med. 2019 May;81(4):380-388. doi: 10.1097/PSY.0000000000000677.
PubMed 31048636
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain and Pain (BaP): Understanding the Central Mechanisms of Pain to Improve Management of Patients With Refractory Chronic Pain
- ClinicalTrials.gov ID
- NCT05099406
- Acronym / sponsor ID
- 2019-PN133
- Conditions
- Chronic Pain
- Keywords
- Transcranial electrical stimulation, Fibromyalgia, Arthritis, Arthrosis, Low back pain, Migraine headaches, Anxiety disorders, Depression
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of Santiago de CompostelaUniversity, hospital or other
- Collaborators
- Ministry of Science and Innovation, Spain, Health Research Institute of Santiago de Compostela - IDIS (Recruitment support), Fundación Biomédica Galicia Sur (Recruitment support)
- Study start
- 1 Jan 2022 (estimated)
- Primary completion
- 1 May 2023 (estimated)
- Study completion
- 1 May 2023 (estimated)
- First posted
- 29 Oct 2021 (actual)
- 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.
Refractory chronic pain represents a serious and limiting health condition which does not respond to standard pharmacological therapy. Thus, it emerges the necessity of new techniques to treat these group of diseases, such as the transcranial electrical stimulation (tES). This procedure induces a low-intensity electrical current through the scalp to modify the excitability of brain cells, thus facilitating changes in neural networks which may be dysfunctional in some chronic pain patients.
The main objective of this research is to test the efficacy of two tES techniques, differentiated by applying direct or alternant electrical current, to reduce the pain intensity and to increase pain thresholds of these patients. Besides, intervention is implemented at home for patients themselves thanks to a portable and convenient stimulator device, after one training session provided by technicians. Researches can supervise the compliance of the treatment remotely, as the stimulator has a permanent connection with their computers. A home-based approach means a more comfortable and accessible treatment alternative for patients, since they do not have to attend to clinics everyday to receive the stimulation; the advantages become even more relevant in the pandemic context, since the risk of being infected is radically minimized.
Despite the main purpose is to test the efficacy of tES to improve the pain suffered by patients, many other areas are considered as secondary end points for being intrinsically linked or affected by the disease, such as the interference in daily tasks provoked by pain, mood disorders (depression/anxiety), fatigue, life quality, physical functioning and sleep quality; these last two variables are measured with actigraph wristwatches, apart from specific questionnaires. Lastly, endogenous modulatory pain mechanisms are examined through sensory tests, namely Conditioned Pain Modulation and Temporal Summation of pain.
Detailed description
This work aims to provide answers to the refractory chronic pain challenge. Pain is defined as refractory when multiple evidence-based biomedical therapies have failed to reach treatment goals that may include adequate pain reduction and/or improvement in daily functioning, even after appropriately assessing and addressing those psychosocial factors that could influence pain outcomes. In this sense, on the one hand, the study focus on detecting central biomarkers of pain modulation and processing which will contribute to improving knowledge of the mechanisms of pain chronification and the diagnosis procedure. On the other hand, given the low efficacy of pharmacological or non-pharmacological therapies for the patients studied, the efficacy of new therapeutic alternatives (tES) is explored. In short, the project will allow the transfer of knowledge to clinical practice in several aspects, such as diagnosis or treatment.
Therefore, the research aims to test the role of defective central pain modulation/processing as explanatory mechanisms for chronic pain. A second main objective is to test the efficacy of transcranial electric stimulation (tES) to modify dysfunction of central mechanism of pain, and to improve symptoms and quality of life in refractory chronic pain patients.
To achieve this, the investigators will select valid and reliable instruments to assess pain and comorbid symptoms in chronic pain patients and the most sensitive outcome measures to assess tES treatment efficacy. Sensory testing paradigms, namely Conditioned Pain Modulation, Temporal Summation of Second Pain and pain-related evoked potentials using electroencephalographic recordings, will act as biomarkers which are proposed to correlate with the severity of the chronic pain disease or some of their symptoms, and also as predictors of the treatment outcome.
Total sample includes 120 patients with refractory pharmaco-resistant pain, attended at the Pain Units of two Public Galician Hospitals (36 male, 84 female).
The study is expected to contribute to detection and preventive measures of future pain, and diagnosis of chronic pain disorders, improving prognosis and development of feasible patient-centered interventions, providing new directions for future research on pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Participants will be randomly assigned to one of three treatment groups (40% active tDCS; 40% Active tACS; 20% Sham). Patients receiving sham stimulation will act as the control group.
| Arm | Type | Receives |
|---|---|---|
| Transcranial direct current stimulation (tDCS) | Active comparator | Device: Transcranial electrical stimulationFifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Current intensity of 2mA is applied during 20 minutes at the left M1, with anodal electrode placed in C3 and cathodal in FP2, following the International 10-20 EEG System. Ramp-up and ramp-down comprises 15 seconds at the beginning and end of the stimulation period. |
| Transcranial alternant current stimulation (tACS) | Active comparator | Device: Transcranial electrical stimulationFifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Two electrodes will be placed at F3 and F4 and connected together for 10-Hz tACS (or the frequency which shows best sensitivity or specificity), and one electrode at Pz will be the return electrode. This setting is used to stimulate the somatosensory cortical region. Stimulation will last for 20 minutes, with a ramp-up and ramp-down of 15 seconds at the beginning and end of the session. |
| Sham stimulation | Placebo comparator | Device: Transcranial electrical stimulationThe electrode montage will be either the tDCS (for half of the participants) or the tACS montage (for the other half), and we will just apply the current at the ramps terms, but no current in the interval between the ramps which practically comprises the whole session. As for the two other group, fifteen sham stimulation sessions will be daily scheduled in a non-interrupted period of two weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Suffering a chronic pain condition of non-cancer nature. Those patients who report chronic pain even after overcoming an oncological process are suitable to participate, but only if they have received the definitive medical discharge and have been free from radiotherapy/chemotherapy for at least twelve months.
- Adult subjects (18-65 years old).
- Subjects able to provide informed consent to participate in the study and to self-report pain.
- Existing chronic pain which reaches an intensity of at least 4 on a 0-10 Numeric Rating Scale (NRS) on average over the past 3 months prior to enrolment.
- Pain intensity of at least 5 on a 0-10 NRS over the week prior to enrolment.
Key exclusion criteria (7 listed)
- Chronic pain derived from current cancer disease.
- Pregnant women or women in fertile age not having efficacious contraception during the whole period of the study.
- History of alcohol or drug abuse within the past 6 months as self-reported.
- Suffering from unstable medical conditions (e.g., uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease).
- Intracranial ferromagnetic devices or implanted stimulator (basal ganglia stimulator, vagus nerve stimulation).
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 |
|---|---|---|
| Transcranial electrical stimulationAlso: Transcranial direct current stimulation, Transcranial alternant current stimulationBy applying a low current over the cortex through the scalp, this technique can excite or inhibit the neural activity, thus modulating brain processes like pain perception and inducing relatively sustained changes in cortical excitability and neuroplasticity. Home-based transcranial electrical stimulation device consists of a custom headgear with fixed electrode sites and built-in cabling made for a simplistic setup for tDCS/tACS stimulation. Systems are equipped with strict dose control feature that provide reliable control over the intensity and timing of stimulation, turning these devices into a feasible and safe clinical alternative. The equipment is specifically designed for easy and simplistic self-setup and allows the researchers to remotely check the position of electrodes and also monitor the stimulation session. | Device | Sham stimulation, Transcranial alternant current stimulation (tACS), Transcranial direct current stimulation (tDCS) |
Primary outcome
Self-reported pain intensity
Time frame: Pre-treatment measure is the average of pain intensity of fifteen days previous to treatment; whereas the post-treatment measure is the average of fifteen days after treatment have finished
Participants must evaluate the intensity of their pain using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the worse the pain is.
14 secondary outcomes
Global severity of chronic pain syndrome
Time frame: Participants will complete MPI one or two days before the treatment onset, and one or two days after treatment ending.
Pressure pain threshold
Time frame: Pressure pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.
Heat pain threshold
Time frame: Heat pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.
Interference in daily living caused by pain
Time frame: Pain interference will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending.
Life quality
Time frame: Life quality will be assessed one or two days before the treatment onset and one or two days after treatment ending.
Physical condition and functioning
Time frame: Estimations about daily energy expenditure, based on sedentary and activity bouts are recorded with wristband actigraphs which participants must wear during the whole research period.
Sleep quality and disturbances
Time frame: Participants will complete PQSI at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending.
Sleep quality and disturbances
Time frame: Wristband actigraph are given to patients fifteen days before the treatment onset, so sleep habits are monitorized since that moment, until fifteen days after treatment have finished
Pain unpleasantness
Time frame: Pre-treatment measure is the average of pain unpleasantness obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished
Mood disorders
Time frame: Participants will complete HADS at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending.
Anxiety
Time frame: Pre-treatment measure is the average of anxiety levels obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished
Fatigue
Time frame: Fatigue is registered with a daily frequency since the fifteen days before the treatment onset, until fifteen days after treatment ending. Participants will complete the MFIS at two time-points, this is, one or two days before and after treatment.
Caregiver burden
Time frame: Caregivers are invited to a face-to-face interview with researchers one or two days before the treatment onset and one or two days after treatment ending.
Global satisfaction with treatment and self-perceived improvement
Time frame: Participants will evaluate their satisfaction with treatment a few days after it had finished.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2021.
- Background: PubMed 30268803Ahn S, Prim JH, Alexander ML, McCulloch KL, Frohlich F. Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study. J Pain. 2019 Mar;20(3):277.e1-277.e11. doi: 10.1016/j.jpain.2018.09.004. Epub 2018 Sep 27.
- Background: PubMed 28709880Antal A, Alekseichuk I, Bikson M, Brockmoller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Floel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19.
- Background: PubMed 20418016Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain. 2010 Jun;149(3):573-581. doi: 10.1016/j.pain.2010.04.003. Epub 2010 Apr 24.
- Background: PubMed 16095934Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-333. doi: 10.1016/j.ejpain.2005.06.009. Epub 2005 Aug 10.
- Background: PubMed 23719569Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013 Jul;14(7):502-11. doi: 10.1038/nrn3516. Epub 2013 May 30.
- Background: PubMed 29391478Choe MK, Lim M, Kim JS, Lee DS, Chung CK. Disrupted Resting State Network of Fibromyalgia in Theta frequency. Sci Rep. 2018 Feb 1;8(1):2064. doi: 10.1038/s41598-017-18999-z.
- Background: PubMed 28884750Davis KD, Flor H, Greely HT, Iannetti GD, Mackey S, Ploner M, Pustilnik A, Tracey I, Treede RD, Wager TD. Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations. Nat Rev Neurol. 2017 Oct;13(10):624-638. doi: 10.1038/nrneurol.2017.122. Epub 2017 Sep 8.
- Background: PubMed 29567583De Keyser R, van den Broeke EN, Courtin A, Dufour A, Mouraux A. Event-related brain potentials elicited by high-speed cooling of the skin: A robust and non-painful method to assess the spinothalamic system in humans. Clin Neurophysiol. 2018 May;129(5):1011-1019. doi: 10.1016/j.clinph.2018.02.123. Epub 2018 Mar 8.
- Background: PubMed 29093972de Tommaso M, Ricci K, Libro G, Vecchio E, Delussi M, Montemurno A, Lopalco G, Iannone F. Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials. Pain Res Treat. 2017;2017:9747148. doi: 10.1155/2017/9747148. Epub 2017 Sep 28.
- Background: PubMed 25530229Duenas M, Salazar A, Ojeda B, Fernandez-Palacin F, Mico JA, Torres LM, Failde I. A nationwide study of chronic pain prevalence in the general spanish population: identifying clinical subgroups through cluster analysis. Pain Med. 2015 Apr;16(4):811-22. doi: 10.1111/pme.12640. Epub 2014 Dec 19.
- Background: PubMed 15621359Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J; IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005 Jan;113(1-2):9-19. doi: 10.1016/j.pain.2004.09.012. No abstract available.
- Background: PubMed 28758313Fallon N, Chiu Y, Nurmikko T, Stancak A. Altered theta oscillations in resting EEG of fibromyalgia syndrome patients. Eur J Pain. 2018 Jan;22(1):49-57. doi: 10.1002/ejp.1076. Epub 2017 Jul 31.
- Individual participant dataSharing planned: No
Related trials for Chronic Pain
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effect of Lumbar Stabilization Exercises With and Without YTWL (Scapular Stabilization Exercises) on Reducing Chronic Low Back Pain and Related Disability. A Randomized Clinical Trial,
Chronic Non Specific Mechanical Low Back Pain
Not yet recruiting
Comparing Non-Medicine Strategies for Improving Low Back Pain
Chronic Low-back Pain (cLBP), High-Impact Chronic Pain (HICP)
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
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.
J. Antonio Vázquez Millán contact
María Teresa Carrillo de la Peña principal investigator
University of Santiago de Compostela
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial electrical stimulation in people with Chronic Pain, run by University of Santiago de Compostela at 1 site in Spain.
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 7 inclusion and 7 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 29 Oct 2021. 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 Spain. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 María Teresa Carrillo de la Peña, PhD (+34 625 76 32 25, mteresa.carrillo@usc.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-reported pain intensity (time frame: Pre-treatment measure is the average of pain intensity of fifteen days previous to treatment; whereas the post-treatment measure is the average of fifteen days after treatment have finished). 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 NCT05099406, which also lists 37 linked publications.
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 29 Oct 2021.