Effects of Transcutaneous Electrical Phrenic Nerve Stimulation and Transcutaneous Electrical Diaphragmatic Stimulation

Official title

Effects of Transcutaneous Electrical Phrenic Nerve Stimulation and Transcutaneous Electrical Diaphragmatic Stimulation: a Randomized Controlled Crossover Trial

Overview

Transcutaneous electrical phrenic nerve stimulation (TEPNS) and transcutaneous electrical diaphragm stimulation (TEDS) are modalities that use surface electrodes placed on the patients' skin to generate action potentials and contractions of the muscle fibers of the diaphragm. The primary objective will be to evaluate the efficacy of TEPNS and TEDS in healthy adult individuals. Secondary objectives will be to assess the feasibility, safety, and level of discomfort reported by the individual resulting from the application of TEPNS and TEDS.

Detailed description

This crossover trial, single-blind, bicentric study will be conducted at two hospitals. Adult volunteers aged 18 to 60 years, healthy, with a body mass index between 18.5 and 24.9 kg/m2, without a history of previous respiratory diseases, and without contraindications to undergo evaluation or application of the proposed electrical stimulation modalities will be included. Participants' diaphragm muscle will be assessed using ultrasound for variables such as thickness, thickness fraction, and diaphragm mobility. Patients will be randomized using opaque envelope draw prior to evaluation into two distinct experimental moments: 1) "TEPNS" moment - application of the TEPNS protocol; or 2) "TEDS" moment - application of the TEDS protocol. Additionally, data regarding the feasibility and safety of the application of electrical stimulation modalities will be collected.

Interventions

• Other Transcutaneous electrical phrenic nerve stimulation (TEPNS)
  The characteristics of the electrical current: biphasic waves, set at a stimulation frequency of 10 Hz, pulse width of 200 μs, rise time of 1.0 second, on time of 1.0 second, fall time of 1.0 second, and off time of 2 seconds, resulting in 12 stimuli per minute. The application of "TEPNS" will initially be performed by defining the trajectory of the phrenic nerve in the cervical region. The negative pole (active point), a stick with a spherical tip for micro-current of 2 mm will be positioned wi
• Other Transcutaneous electrical diaphragm stimulation (TEDS)
  The characteristics of the electrical current are: biphasic waves, set at a stimulation frequency of 30 Hz, pulse width of 400 μs, rise time of 1.0 second, on time of 1.0 second, fall time of 1.0 second, and off time of 2 seconds, resulting in 12 stimuli per minute. Two self-adhesive electrodes sized (5.0 x 5.0 cm) will be used, positioned in the bilateral parasternal region next to the xiphoid process and the other electrode in the intercostal space between the 6th and 7th ribs bilaterally, at

Primary outcome measures

• Diaphragm mobility [Time frame: At baseline, between the fourth and fifth minutes and between the ninth and tenth minutes after the start of stimulation.]
• Diaphragm thickness [Time frame: At baseline, between the fourth and fifth minutes and between the ninth and tenth minutes after the start of stimulation.]
• Thickening fraction [Time frame: At baseline, between the fourth and fifth minutes and between the ninth and tenth minutes after the start of stimulation.]

Secondary outcome measures (2)

• Evaluation of sensory discomfort [Time frame: At baseline, five and 10 minutes the start of stimulation.]
• Safety of TEPNS and TEDS application [Time frame: The events will be monitored throughout the entire period of TEPNS and TEDS application.]

Eligibility criteria

Inclusion criteria

• Age between 18 and 60 years;
• Normal pulmonary function test, without alterations, assessed through spirometry;
• Body Mass Index (BMI) between 18.5 and 24.9 kg/m2.

Exclusion criteria

• Smokers or former smokers;
• Individuals with previously known cardiopulmonary diseases (restrictive lung diseases, chronic obstructive pulmonary disease - COPD, asthma, cystic fibrosis, among other pathologies);
• Presence of implanted electrical devices (pacemaker, implantable cardioverter-defibrillator, among others);
• Individuals who have contraindications to undergo evaluation and/or application of transcutaneous electrical stimulation of the diaphragm muscle, such as: altered sensitivity, wounds at the site of application, deformities, among other conditions.

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

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Treatment

Study locations

Brazil · 1 center

• Hospital Sírio Libanês — São Paulo

Publications

• Boon AJ, Harper CJ, Ghahfarokhi LS, Strommen JA, Watson JC, Sorenson EJ. Two-dimensional ultrasound imaging of the diaphragm: quantitative values in normal subjects. Muscle Nerve. 2013 Jun;47(6):884-9. doi: 10.1002/mus.23702. Epub 2013 Apr 29. PMID 23625789
• Cancelliero-Gaiad KM, Ike D, Pantoni CB, Mendes RG, Borghi-Silva A, Costa D. Acute effects of transcutaneous electrical diaphragmatic stimulation on respiratory pattern in COPD patients: cross-sectional and comparative clinical trial. Braz J Phys Ther. 2013 Nov-Dec;17(6):547-55. doi: 10.1590/S1413-35552012005000121. Epub 2013 Nov 14. PMID 24271095
• Canella C, Demondion X, Delebarre A, Moraux A, Cotten H, Cotten A. Anatomical study of phrenic nerve using ultrasound. Eur Radiol. 2010 Mar;20(3):659-65. doi: 10.1007/s00330-009-1579-z. Epub 2009 Sep 2. PMID 19727747
• Carrillo-Esper R, Perez-Calatayud AA, Arch-Tirado E, Diaz-Carrillo MA, Garrido-Aguirre E, Tapia-Velazco R, Pena-Perez CA, Espinoza-de Los Monteros I, Meza-Marquez JM, Flores-Rivera OI, Zepeda-Mendoza AD, de la Torre-Leon T. Standardization of Sonographic Diaphragm Thickness Evaluations in Healthy Volunteers. Respir Care. 2016 Jul;61(7):920-4. doi: 10.4187/respcare.03999. Epub 2016 Apr 12. PMID 27072012
• Hedenstierna G, Tokics L, Lundquist H, Andersson T, Strandberg A, Brismar B. Phrenic nerve stimulation during halothane anesthesia. Effects of atelectasis. Anesthesiology. 1994 Apr;80(4):751-60. doi: 10.1097/00000542-199404000-00006. PMID 8024128
• Santana PV, Cardenas LZ, Albuquerque ALP, Carvalho CRR, Caruso P. Diaphragmatic ultrasound: a review of its methodological aspects and clinical uses. J Bras Pneumol. 2020 Nov 20;46(6):e20200064. doi: 10.36416/1806-3756/e20200064. eCollection 2020. PMID 33237154
• Testa A, Soldati G, Giannuzzi R, Berardi S, Portale G, Gentiloni Silveri N. Ultrasound M-mode assessment of diaphragmatic kinetics by anterior transverse scanning in healthy subjects. Ultrasound Med Biol. 2011 Jan;37(1):44-52. doi: 10.1016/j.ultrasmedbio.2010.10.004. PMID 21144957
• Mol CG, Nawa RK, Britto ACDC, Eid RAC, Campos EC, Saraiva LT, Righetti RF, Yamaguti WP. Effects of transcutaneous electrical phrenic nerve stimulation and transcutaneous electrical diaphragmatic stimulation: A protocol for a randomized, single-blind, crossover trial. PLoS One. 2026 Apr 27;21(4):e0347493. doi: 10.1371/journal.pone.0347493. eCollection 2026. PMID 42044135

Identifiers

NCT: NCT06339632 · AVAP-NG 3363

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗