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| Name | Class |
|---|---|
| University of Sao Paulo General Hospital | OTHER |
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This project protocol investigates the efficacy of transcranial direct current stimulation (tDCS) in treating neuropathic pain and improving sleep quality among Brazilian military personnel. Given the high prevalence of chronic pain and sleep disturbances in this population, and the limitations of current pharmacological treatments, our randomized, triple-blinded, sham-controlled trial explores the potential of tDCS as a non-invasive therapeutic intervention. The results of this study could have a significant impact on improving the well-being and performance of military personnel, while also reducing healthcare costs associated with long-term medication use.
The intervention will be carried out into two-weeks daily consecutive sessions of 20 minutes each, with 1 session per day, and a weekend interval. Direct current stimulation will be administered through an electrical stimulator model MicroEstim Genius (NKL), Brusque, Brazil. During the session, the participants will be awake and seated in a comfortable seat. The environment will be air-conditioned, free of visual and auditory stimuli.
The sessions will be conducted by a trained health professional. The groups will receive single-phase direct current with an intensity of 2 mA up, according to data presented by Pacheco-Barrios et al. (2021). Electrodes with a size of 35cm² (5 x 7 centimeters) will be used. Electrodes will be placed on the scalp, fixed with elastic bands, and immersed in 10 to 12 mL of saline solution.
The electrode montage will be performed for one of two possible targets: anodal stimulation over DLPFC or anodal stimulation over M1, and also sham in both targets according to the participants' designations after randomization to one of the three groups.
The device displays will be identical across active and sham groups, and to ensure blinding, an active current will be applied for 30 seconds at the beginning and end of the sham stimulation to mimic the sensation of the current ramp experienced in active stimulation. Stimulations of less than 3 minutes of tDCS do not induce cortical excitability effects, according to Nitsche and Paulus (2000), being safely inactive for the expected results.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anodal tdcs over the primary motor (M1) | Active Comparator | Anode placement will be positioned over M1, using the international 10-20 EEG system (C3/C4 for left or right M1). Cathode placement will be on the contralateral supraorbital area (above the eyebrow) to complete the circuit. |
|
| Anodal tdcs over the dorsolateral prefrontal cortex (DLPFC) | Active Comparator | Anode placement positioned over dorsolateral prefrontal cortex (DLPFC), using the international 10-20 EEG system (F3/F4 for left or right DLPFC). Cathode placement will be on the contralateral supraorbital area (above the eyebrow) to complete the circuit. |
|
| sham tdcs over M1 or DLPFC | Sham Comparator | The sham group will be divided in half of participants with Sham M1 and the other half as Sham DLPFC. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tDCS | Device | This group will receive single-phase direct current with an intensity of 2 mA up. Electrodes with a size of 35cm² (5 x 7 centimeters) will be used. Electrodes will be placed on the scalp, fixed with elastic bands, and immersed in 10 to 12 mL of saline solution. |
| Measure | Description | Time Frame |
|---|---|---|
| pain intensity by VAS | The primary outcome is a reduction in pain intensity by at least 30% (Dworkim et al., 2004; Farrar et al 2001). It will be assessed using the 100 mm Visual Analogue Scale (VAS), which consists of straight lines 100 mm long indicating "no pain" on one end and "worst possible pain or most intense pain possible" on the other (Huskisson, 1974). The VAS is scored by measuring the distance from the "no pain" end of the line. Pain intensity will be assessed daily during the 10day intervention. | at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Pittsburgh Sleep Quality Index (PSQI) | Before and after the interventions, sleep secondary outcomes will be assessed using the Pittsburgh Sleep Quality Index (PSQI), which global score ranges from 0 to 21, with a higher score indicating poorer sleep quality. Each of the 7 component scores also range from 0 to 3, where a higher score on each component signifies more difficulty. | It will be measured at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Pittsburgh Sleep Quality Index Addendum for Posttraumatic Stress Disorder (PSQI-A) | A possible confounder to be controlled for will be assessed by the Pittsburgh Sleep Quality Index Addendum for Posttraumatic Stress Disorder (PSQI-A) addresses patients exposed to trauma and was validated in U.S. male military veterans (Insana et al., 2013) and also in Portuguese by Gonçalves and Lima (2014). Seven items assess the frequency of hot flashes; general nervousness; memories or nightmares of the traumatic experience; severe anxiety or panic, not related to traumatic memories; nightmares, not related to traumatic memories; episodes of terror or screaming during sleep without full awakening; and episodes of staged dreams (Germain et al., 2005). The PSQI-A (Pittsburgh Sleep Quality Index Addendum for Posttraumatic Stress Disorder) ranges from 0 to 21. Higher scores indicate a poorer outcome in PTSD symptom severity and a worse sleep quality. Scores of 5 or less generally indicate good sleep quality. Higher scores on the PSQI-A are also associated with more combat exposure. |
Inclusion criteria:
Exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eline RF Barbosa, MD, MD | Contact | +5562981787456 | elinebarbosa@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Clarissa Bueno, MD, PhD | São Paulo University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital da PolÃcia Militar de Goiás | Goiânia | Goiás | 74423-120 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16564618 | Background | Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006 May;122(1-2):197-209. doi: 10.1016/j.pain.2006.02.023. Epub 2006 Mar 27. | |
| 10990547 |
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All individual participant data will be available, after de-identification. There will be shared the study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code.
after one year of the publication of the main results (2030 March) - for 3 years.
Data will be shared with researchers upon request for analyses related to the study's objectives, via a secure data repository.
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| ID | Term |
|---|---|
| D009437 | Neuralgia |
| D007319 | Sleep Initiation and Maintenance Disorders |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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The intervention will be carried out into two-weeks daily consecutive sessions of 20 minutes each, with 1 session/day, and a weekend interval. Direct current stimulation will be administered through an electrical stimulator model MicroEstim Genius (NKL), Brusque, Brazil. During the session, the participants will be awake and seated in a comfortable seat. The environment will be air-conditioned, free of visual and auditory stimuli.
The sessions will be conducted by a trained health professional. The groups will receive single-phase direct current with an intensity of 2 mA up, according to data presented by Pacheco-Barrios et al. (2021). Electrodes with a size of 35cm² (5 x 7 centimeters) will be used. Electrodes will be placed on the scalp, fixed with elastic bands, and immersed in 10 to 12 mL of saline solution.
The electrode montage will be performed for one of two possible targets: anodal stimulation over DLPFC or anodal stimulation over M1, and also sham in both targets.
Not provided
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A triple-blinding strategy will be implemented, including participants and outcome assessors, as well as staff responsible for recruitment and statistical analysis. To ensure proper intervention, only the health professional administering the treatment will know each participant's assigned group.
|
| sham intervention | Device | The device displays will be identical across active and sham groups, and to ensure blinding, an active current will be applied for 30 seconds at the beginning and end of the sham stimulation to mimic the sensation of the current ramp experienced in active stimulation. Stimulations of less than 3 minutes of tDCS do not induce cortical excitability effects, according to Nitsche and Paulus (2000), being safely inactive for the expected results. |
|
| Epworth Sleepiness Scale (ESS) | Before and after the interventions, the Epworth Sleepiness Scale (ESS) will be applied. The ESS has a minimum score of 0 and a maximum score of 24. Higher scores indicate greater daytime sleepiness, with scores above 10 suggesting excessive daytime sleepiness. A higher score is therefore indicative of a worse outcome, as it signifies a greater tendency to fall asleep in various situations. | at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. |
| the Visual Analogue Scale for Fatigue Severity (VAS-F) | Before and after the interventions, we will apply the Visual Analogue Scale for Fatigue Severity (VAS-F). The VAS-F uses a 100 mm line and scores are determined by measuring the distance from one end of the line to the point the individual marks, resulting in a score between 0 and 100. A higher score indicates greater fatigue severity. | measured at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. |
| Polysomnographic evaluation - time | Sleep evaluation with Type 2 polysomnography (PSG) will be recorded at baseline and will access time in bed (minutes), time to sleep onset (minutes), total sleep time (minutes), sleep latency (minutes), REM latency (minutes), wake after sleep onset (minutes). | PSG will be measured at baseline and at the end of the ten-day treatment. |
| Polysomnographic evaluation - arousal index | The Arousal Index (AI) in polysomnography will be measured by counting the total number of arousals during sleep and dividing it by the total sleep time. | PSG will be measured at baseline and at the end of the ten-day treatment. |
| Polysomnographic evaluation - sleep efficiency | Sleep efficiency (SE) will be calculated as the total sleep time (TST) divided by the total time in bed, multiplied by 100. A higher SE percentage indicates that more time in bed is spent actually sleeping. Normal sleep efficiency is generally considered to be 85% or higher. | PSG will be measured at baseline, at the end of the ten-day treatment. |
| Polysomnographic evaluation- sleep stages | Sleep stages will be scored by analyzing 30-second epochs of polysomnographic recordings using electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) signals. | at baseline, at the end of the ten-day treatment. |
| Polysomnographic evaluation- PLMI | The Periodic Limb Movement Index (PLMI) is calculated as the number of periodic limb movements during sleep (PLMS) per hour of sleep time. According to the American Academy of Sleep Medicine (AASM) scoring criteria, a limb movement (LM) is scored if there is an increase in anterior tibialis electromyogram (EMG) activity of more than 8 microvolts above resting EMG, lasting between 0.5 to 10 seconds. Periodic limb movements (PLMS) are defined as a series of at least four consecutive limb movements, each separated by an inter-movement interval of 5 to 90 seconds. The PLMI is computed by dividing the total number of PLMS by the total sleep time in hours, yielding PLMS per hour of sleep (PLMS/h). A PLMI greater than 15 per hour in adults is considered clinically significant for periodic limb movement disorder. | PSG will be measured at baseline, at the end of the ten-day treatment. |
| at baseline and at the end of 10-day treatment |
| the Depression-Anxiety-Stress Scales-21 (DASS-21) | Possible confounders to be controlled for will be assessed by the Depression-Anxiety-Stress Scales-21 (DASS-21) validated for Portuguese (Lovibond and Lovibond, 1995; Vignola and Tucci, 2014), that measures the levels of depression, anxiety and stress based on behaviors and feelings experienced in the last seven days. The DASS-21 has a score range from 0 to 63, in which the total score is calculated by summing the scores from all three subscales (depression, anxiety and stress). Higher scores indicate a more severe or frequent experience of depression, anxiety, and stress symptoms, i.e., a worse outcome. | at baseline and at the end of 10-day treatment |
| Sociodemografic characteristics - DOB | The sociodemographic data collected will include date of birth (DD/MM/YYYY) | at baseline |
| Sociodemografic characteristics - age | The sociodemographic data collected will include age (years) | at baseline |
| Sociodemografic characteristics - educational level | The sociodemographic data collected will include educational level (length in years). | at baseline |
| Sociodemografic characteristics - marital status | The sociodemographic data collected will include marital status (single, married, widow, other) | at baseline |
| Sociodemografic characteristics - previous diseases | The sociodemographic data collected will include pre-existing diagnoses (name of the disease) | at baseline |
| Sociodemografic characteristics - medication use | The sociodemographic data collected will include medication currently and previously used that may interfere with the results. | at baseline |
| Sociodemografic characteristics- weight | Weight (kilograms) will be measured in a scale in the baseline. | at baseline |
| sociodemografic characteristics- height | Height will be measured in centimeters with a height and weight scale, in which a sliding bar that is lowered to touch the top of the person's head, and the measurement is then read from the scale's markings. In addition, weight and height will be combined to report body mass index- BMI - in kg/m2. | at baseline |
| Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x. |
| 26193817 | Background | Mehta S, McIntyre A, Guy S, Teasell RW, Loh E. Effectiveness of transcranial direct current stimulation for the management of neuropathic pain after spinal cord injury: a meta-analysis. Spinal Cord. 2015 Nov;53(11):780-5. doi: 10.1038/sc.2015.118. Epub 2015 Jul 21. |
| 32845195 | Background | Pacheco-Barrios K, Cardenas-Rojas A, Thibaut A, Costa B, Ferreira I, Caumo W, Fregni F. Methods and strategies of tDCS for the treatment of pain: current status and future directions. Expert Rev Med Devices. 2020 Sep;17(9):879-898. doi: 10.1080/17434440.2020.1816168. Epub 2020 Sep 15. |
| 11690728 | Background | Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9. |
| D009461 |
| Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D001523 | Mental Disorders |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |