Neuropathic Pain Intervention With tDCS in Brazilian Military Personnel (NeuBRAIN Trial)

Official title

Neuropathic Pain Intervention With tDCS in Brazilian Military Personnel Randomized Controlled Trial

Overview

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

• Device tDCS
  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.
• Device sham 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.

Primary outcome measures

• pain intensity by VAS [Time frame: at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention.]

Secondary outcome measures (8)

• Pittsburgh Sleep Quality Index (PSQI) [Time frame: It will be measured at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention.]
• Epworth Sleepiness Scale (ESS) [Time frame: 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) [Time frame: measured at baseline, at the end of the ten-day treatment and at follow-up, three weeks post-intervention.]
• Polysomnographic evaluation - time [Time frame: PSG will be measured at baseline and at the end of the ten-day treatment.]
• Polysomnographic evaluation - arousal index [Time frame: PSG will be measured at baseline and at the end of the ten-day treatment.]
• Polysomnographic evaluation - sleep efficiency [Time frame: PSG will be measured at baseline, at the end of the ten-day treatment.]
• Polysomnographic evaluation- sleep stages [Time frame: at baseline, at the end of the ten-day treatment.]
• Polysomnographic evaluation- PLMI [Time frame: PSG will be measured at baseline, at the end of the ten-day treatment.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Brazil · 1 center

• Hospital da Polícia Militar de Goiás — Goiânia

Publications

• 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. PMID 16564618
• 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. PMID 10990547
• 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. PMID 26193817
• 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. PMID 32845195
• 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. PMID 11690728

Identifiers

NCT: NCT06994390 · NeuBRAIN RCT protocol

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗