Neuropathic Pain, Sleep Quality, Transcranial Direct Current Stimulation
Conditions
Keywords
transcranial current stimulation, neuropathic pain, sleep
Brief summary
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.
Detailed description
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.
Interventions
DEVICEtDCS
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.
DEVICEsham intervention
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.
Sponsors
Hospital das Clínicas de São Paulo - SP
Hospital da Polícia Militar de Goiás
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Military personnel (active and veterans) with chronic pain due to central or peripheral neuropathy and poor sleep quality; * Age over 18 years old; * Defined chronic NeP according to current guidelines (ICD-10 codes OR DN-4); * Pain with an average intensity score above 40/100 mm on a visual analogue scale (VAS); * Medication stability (chronic pain, depression, anxiety, sleep) for at least six weeks; * Patients with bad sleep quality identified by the Pittsburgh Sleep Quality Index (PSQI) of 5 or more who do not improve under conventional treatment.
Exclusion criteria
* General contraindications for tDCS: past head trauma, current epilepsy, intracranial ferromagnetic components, pacemaker, implanted microprocessors (i.e., cochlear implants); * Pregnancy; * Known major psychiatric disorders (as assessed by the DSM-5, e.g., psychosis), history of substance abuse, or work litigation issues; * History of chronic refractory migraines; * Non-treated moderate to severe sleep apnea defined as apnea/hypopnea index greater than 15 events per hour in baseline polysomnography; * Skin conditions such as psoriasis or eczema that involve the scalp (Thair et al, 2017); * Cancer-related pain; * BMI \>35, due to increased reports of pain associated with increased BMI (Basem, et al., 2021; Stokes et al., 2020); * Patients who do not sign informed consent or do not want to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pain intensity by VAS | at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epworth Sleepiness Scale (ESS) | at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. | 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. |
| the Visual Analogue Scale for Fatigue Severity (VAS-F) | measured at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. | 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. |
| Polysomnographic evaluation - time | PSG will be measured at baseline and at the end of the ten-day treatment. | 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). |
| Pittsburgh Sleep Quality Index (PSQI) | It will be measured at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention. | 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. |
| Polysomnographic evaluation - sleep efficiency | PSG will be measured at baseline, at the end of the ten-day treatment. | 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. |
| Polysomnographic evaluation- sleep stages | at baseline, at the end of the ten-day treatment. | Sleep stages will be scored by analyzing 30-second epochs of polysomnographic recordings using electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) signals. |
| Polysomnographic evaluation- PLMI | PSG will be measured at baseline, at the end of the ten-day treatment. | 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. |
| Polysomnographic evaluation - arousal index | PSG will be measured at baseline and at the end of the ten-day treatment. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sociodemografic characteristics - DOB | at baseline | The sociodemographic data collected will include date of birth (DD/MM/YYYY) |
| sociodemografic characteristics- height | at baseline | 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. |
| Sociodemografic characteristics - age | at baseline | The sociodemographic data collected will include age (years) |
| Pittsburgh Sleep Quality Index Addendum for Posttraumatic Stress Disorder (PSQI-A) | at baseline and at the end of 10-day treatment | 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. |
| the Depression-Anxiety-Stress Scales-21 (DASS-21) | at baseline and at the end of 10-day treatment | 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. |
| Sociodemografic characteristics - educational level | at baseline | The sociodemographic data collected will include educational level (length in years). |
| Sociodemografic characteristics - marital status | at baseline | The sociodemographic data collected will include marital status (single, married, widow, other) |
| Sociodemografic characteristics - previous diseases | at baseline | The sociodemographic data collected will include pre-existing diagnoses (name of the disease) |
| Sociodemografic characteristics - medication use | at baseline | The sociodemographic data collected will include medication currently and previously used that may interfere with the results. |
| Sociodemografic characteristics- weight | at baseline | Weight (kilograms) will be measured in a scale in the baseline. |
Countries
Brazil
Contacts
Primary ContactEline RF Barbosa, MD, MD
Outcome results
None listed