Transcutaneous Vagal Stimulation in Knee Osteoarthritis (TRAVKO): Protocol of a Superiority, Outcome Assessor- and Participant-Blind, Randomised Controlled Trial
Abstract
:1. Introduction
Objective
2. Materials and Methods
2.1. Ethical Considerations and Trial Registration
2.2. Design
2.3. Assessments
2.4. Study Population, Recruitment and Assignment
2.5. Groups & Randomisation
2.6. Masking
2.7. Sample Size
2.8. Selection Criteria
3. Results
3.1. Descriptive Data
3.2. Primary Outcome
3.3. Secondary Outcomes
3.4. Other Measurements
3.5. Procedures
3.5.1. Evaluations
3.5.2. Interventions
3.6. Data Analysis
3.7. Role of the Funding Source
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A. Exercise Protocol
The exercise protocol is guided by general principles described below: 1.- The exercises should not increase the patient’s pain significantly. They can cause fatigue and a feeling of tiredness, but they should not increase the symptoms significantly; that is, if the patient feels the same pain when doing the exercise as when resting, he/she can do it without pain or with mild pain (VAS 30 mm. approximately). 2.- If a patient can exercise at one level without increasing their basal pain, he/she move to the next level. If the next level causes increased pain, the level should be decreased. 3.- Emphasis should be placed on the quality of the exercises’ execution and not on the repetitions or series. If a patient performs the exercise inappropriately, an attempt should be made to correct it. Stop the exercise if the patient is not able to continue with quality repetitions, that is, without compensation and in a coordinated and fluid manner. The patient should not perform apnea in isometric exercises. All exercises have the transversal objective of reducing pain. | |||||
Objective | Level 1 | Level 2 | Level 3 | Level 4 | Level 5 |
Objective: To strengthen the quadriceps | Patient in a seated position. Isometric contraction of the quadriceps with the extended leg. Hold for 10 s and perform 10 repetitions. Alternating both legs. | Patient in supine position. Lifting of the extended leg. Hold for 10 s and perform 10 repetitions. Alternating both legs. | Patient in supine position. Lifting of the extended leg. Hold for 10 s and perform 10 repetitions with 2 kg at the distal part of the leg. Alternating both legs. | Patient in seated position. Knee extension with 2 kg at the distal part of the leg. 10 repetitions × 3 series. Alternating both legs. | Patient in seated position. Knee extension with 4 kg at the distal part of the leg. 10 repetitions × 3 series. Alternating both legs. |
Objective: To strengthen the hamstrings | Patient in prone position. Knee flexion with no weights. 10 repetitions × 3 series. Alternating both extremities. | Patient in prone position. Knee flexion with 1 kg at the distal part of the leg. 10 repetitions × 3 series. Alternating both extremities. | Patient in standing position. Knee flexion with 1 kg at the distal part of the leg. 10 repetitions × 3 series. Alternating both extremities. | Patient in standing position. Knee flexion with 2 kg at the distal part of the leg. 10 repetitions × 3 series. Alternating both extremities. | Patient in standing position. Knee flexion with 4 kg at the distal part of the leg. 20 reps × 3 sets. Alternating both extremities. |
Objective: To strengthen the gluteus maximus | Patient in prone position. Isometric contraction of the gluteus maximus with posterior extended leg lift. Hold for 10 s and perform 10 repetitions. Alternating both extremities. | Double leg supine bridge. Hold for 5 s and perform 10 repetitions. | Double leg supine bridge. Hold for 10 s and perform 10 repetitions. | Single leg supine bridge. Hold for 10 s and perform 10 repetitions. Alternating both extremities. | Single leg supine bridge whit unstable surface. Hold for 10 s and perform 20 repetitions. Alternating both extremities. |
Objective: To strengthen the gluteus medius | Patient in lateral decubitus position. External rotation of the hip, with hip and knee flexion (clamshell exercise). 10 repetitions × 3 series. Alternating both extremities. | Patient in lateral decubitus position. Isometric lateral extended leg lift. Hold for 3 to 5 s × 10 repetitions. Alternating both extremities. | Patient in lateral decubitus position. Isometric lateral extended leg lift. 10 s × 10 repetitions. Alternating both extremities. | Patient in lateral decubitus position. Isotonic lateral extended leg lift. 10 repetitions × 3 series. Alternating both extremities. | Patient in lateral decubitus position. Isotonic lateral extended leg lift with 1 kg at the distal part of the leg. 10 repetitions × 3 series. Alternating both extremities. |
Objective: To strengthen the lumbo-abdominal area | Patient in 4 prone position. Lifting of leg. Hold for 3 to 5 s and perform 10 repetitions. Alternating both extremities. | Bird dog. Hold for 3 to 5 s and perform 10 repetitions. Alternating every diagonal. | Bird dog. Hold for 10 s and perform 10 repetitions. Alternating every diagonal. | Knee prone bridge. Hold for 5 to 10 s and perform 10 repetitions. | Prone bridge. Hold for 5 to 10 s and perform 10 repetitions. |
Objective: Co-contraction at CCC | Double-leg squats with parallel support. 10 repetitions × 3 series. | Double-leg squats. 10 repetitions × 3 series. | Single-leg squats 10 repetitions × 3 series. Alternating both extremities. | Single-leg squats. 20 reps × 3 sets. Alternating both extremities. | Single-leg squats. 30 repetitions × 3 series. Alternating both extremities. |
Objective: Increase or maintain aerobic capacity | Cyclorgometer 10 min. individual ‘tolerance | Cyclorgometer 10 min. 9–10 Borg scale | Cyclorgometer 10 min. 11–12 Borg scale | Cyclorgometer 10 min. 13–14 Borg scale | Cyclorgometer 10 min. 15–16 Borg scale |
Objective: Increase knee flexo-extension range | Patient in supine position, hip flexion with extended knee and band assistance to stretch hamstring muscles (2 repetitions of 30 s). Patient in supine position, knees to chest with the assistance of his/her arms to stretch gluteal and lumbar muscles (2 repetitions of 30 s). Patient in prone position, knee flexion with band assistance for stretching the quadriceps muscle (2 repetitions of 30 s). It should be noted that all stretches should be up to the feeling of tension and with no increase in pain. |
References
- Spitaels, D.; Mamouris, P.; Vaes, B.; Smeets, M.; Luyten, F.; Hermens, R.; Vankrunkelsven, P. Epidemiology of knee osteoarthritis in general practice: A registry-based study. BMJ Open 2020, 10, e031734. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nicholls, E.; Thomas, E.; van der Windt, D.A.; Croft, P.R.; Peat, G. Pain trajectory groups in persons with, or at high risk of, knee osteoarthritis: Findings from the Knee Clinical Assessment Study and the Osteoarthritis Initiative. Osteoarthr. Cartil. 2014, 22, 2041–2050. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heidari, B. Knee osteoarthritis prevalence, risk factors, pathogenesis and features: Part I. Casp. J. Intern. Med. 2011, 2, 205–212. [Google Scholar]
- Cui, A.; Li, H.; Wang, D.; Zhong, J.; Chen, Y.; Lu, H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine 2020, 29–30, 100587. [Google Scholar] [CrossRef]
- Altman, R.D. Early management of osteoarthritis. Am. J. Manag. Care 2010, 16 (Suppl. M), S41–S47. [Google Scholar]
- Hawker, G.A. Osteoarthritis is a serious disease. Clin. Exp. Rheumatol. 2019, 37 (Suppl. 1), 3–6. [Google Scholar]
- Case, J.P.; Baliunas, A.J.; Block, J.A. Lack of Efficacy of Acetaminophen in Treating Symptomatic Knee Osteoarthritis. Arch. Intern. Med. 2003, 163, 169. [Google Scholar] [CrossRef] [Green Version]
- Conaghan, P.G.; Peloso, P.M.; Everett, S.V.; Rajagopalan, S.; Black, C.M.; Mavros, P.; Arden, N.K.; Phillips, C.J.; Rannou, F.; van de Laar, M.A.F.J.; et al. Inadequate pain relief and large functional loss among patients with knee osteoarthritis: Evidence from a prospective multinational longitudinal study of osteoarthritis real-world therapies. Rheumatology 2015, 54, 270–277. [Google Scholar] [CrossRef] [Green Version]
- Moseley, J.B.; O’Malley, K.; Petersen, N.J.; Menke, T.J.; Brody, B.A.; Kuykendall, D.H.; Hollingsworth, J.C.; Ashton, C.M.; Wray, N.P. A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee. N. Engl. J. Med. 2002, 347, 81–88. [Google Scholar] [CrossRef]
- Kirkley, A.; Birmingham, T.B.; Litchfield, R.B.; Giffin, J.R.; Willits, K.R.; Wong, C.J.; Feagan, B.G.; Donner, A.; Griffin, S.H.; D’Ascanio, L.M.; et al. A Randomized Trial of Arthroscopic Surgery for Osteoarthritis of the Knee. N. Engl. J. Med. 2008, 359, 1097–1107. [Google Scholar] [CrossRef]
- Brosseau, L.; Taki, J.; Desjardins, B.; Thevenot, O.; Fransen, M.; Wells, G.A.; Mizusaki Imoto, A.; Toupin-April, K.; Westby, M.; Álvarez Gallardo, I.C.; et al. The Ottawa panel clinical practice guidelines for the management of knee osteoarthritis. Part two: Strengthening exercise programs. Clin. Rehabil. 2017, 31, 596–611. [Google Scholar] [CrossRef] [PubMed]
- Fransen, M.; McConnell, S.; Harmer, A.R.; Van der Esch, M.; Simic, M.; Bennell, K.L. Exercise for osteoarthritis of the knee: A Cochrane systematic review. Br. J. Sports Med. 2015, 49, 1554–1557. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- da Graca Lopes Tarragó, M.; Deitos, A.; Brietzke, A.P.; Vercelino, R.; Torres, I.L.S.; Fregni, F.; Caumo, W. Descending Control of Nociceptive Processing in Knee Osteoarthritis Is Associated With Intracortical Disinhibition. Medicine 2016, 95, e3353. [Google Scholar] [CrossRef] [PubMed]
- Caumo, W.; Deitos, A.; Carvalho, S.; Leite, J.; Carvalho, F.; Dussán-Sarria, J.A.; da Graca Lopes Tarragó, M.; Souza, A.; da Silva Torres, I.L.; Fregni, F. Motor Cortex Excitability and BDNF Levels in Chronic Musculoskeletal Pain According to Structural Pathology. Front. Hum. Neurosci. 2016, 10, 357. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frøkjaer, J.B.; Bergmann, S.; Brock, C.; Madzak, A.; Farmer, A.D.; Ellrich, J.; Drewes, A.M. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. Neurogastroenterol. Motil. 2016, 28, 592–598. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Courties, A.; Deprouw, C.; Maheu, E.; Gibert, E.; Gottenberg, J.-E.; Champey, J.; Banneville, B.; Chesnel, C.; Amarenco, G.; Rousseau, A.; et al. Effect of Transcutaneous Vagus Nerve Stimulation in Erosive Hand Osteoarthritis: Results from a Pilot Trial. J. Clin. Med. 2022, 11, 1087. [Google Scholar] [CrossRef]
- Katz, P.S.; Calin, R.J. Neuromodulation. Encycl. Neurosci. 2009, 6, 497–503. [Google Scholar]
- Busch, V.; Zeman, F.; Heckel, A.; Menne, F.; Ellrich, J.; Eichhammer, P. The effect of transcutaneous vagus nerve stimulation on pain perception—An experimental study. Brain Stimul. 2013, 6, 202–209. [Google Scholar] [CrossRef]
- Nesbitt, A.D.; Marin, J.C.A.; Tompkins, E.; Ruttledge, M.H.; Goadsby, P.J. Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment. Neurology 2015, 84, 1249–1253. [Google Scholar] [CrossRef]
- Randich, A.; Aicher, S.A. Medullary substrates mediating antinociception produced by electrical stimulation of the vagus. Brain Res. 1988, 445, 68–76. [Google Scholar] [CrossRef]
- Nishikawa, Y.; Koyama, N.; Yoshida, Y.; Yokota, T. Activation of ascending antinociceptive system by vagal afferent input as revealed in the nucleus ventralis posteromedialis. Brain Res. 1999, 833, 108–111. [Google Scholar] [CrossRef] [PubMed]
- Berthoud, H.-R.; Neuhuber, W.L. Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. 2000, 85, 1–17. [Google Scholar] [CrossRef]
- Borovikova, L.V.; Ivanova, S.; Zhang, M.; Yang, H.; Botchkina, G.I.; Watkins, L.R.; Wang, H.; Abumrad, N.; Eaton, J.W.; Tracey, K.J. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000, 405, 458–462. [Google Scholar] [CrossRef] [PubMed]
- Lauwers, M.; Courties, A.; Sellam, J.; Wen, C. The cholinergic system in joint health and osteoarthritis: A narrative-review. Osteoarthr. Cartil. 2021, 29, 643–653. [Google Scholar] [CrossRef] [PubMed]
- Woodell-May, J.E.; Sommerfeld, S.D. Role of Inflammation and the Immune System in the Progression of Osteoarthritis. J. Orthop. Res. 2020, 38, 253–257. [Google Scholar] [CrossRef] [PubMed]
- Napadow, V.; Edwards, R.R.; Cahalan, C.M.; Mensing, G.; Greenbaum, S.; Valovska, A.; Li, A.; Kim, J.; Maeda, Y.; Park, K.; et al. Evoked Pain Analgesia in Chronic Pelvic Pain Patients Using Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation. Pain Med. 2012, 13, 777–789. [Google Scholar] [CrossRef]
- Barbanti, P.; Grazzi, L.; Egeo, G.; Padovan, A.M.; Liebler, E.; Bussone, G. Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: An open-label study. J. Headache Pain 2015, 16, 61. [Google Scholar] [CrossRef] [Green Version]
- Dreiser, R.L.; Maheu, E.; Guillou, G.B.; Caspard, H.; Grouin, J.M. Validation of an algofunctional index for osteoarthritis of the hand. Rev. Rhum. Engl. Ed. 1995, 62, 43S–53S. [Google Scholar]
- World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013, 310, 2191–2194. [Google Scholar] [CrossRef] [Green Version]
- Schulz, K.F.; Altman, D.G.; Moher, D.; CONSORT Group. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. BMJ 2010, 340, c332. [Google Scholar] [CrossRef]
- Chan, A.-W.; Tetzlaff, J.M.; Altman, D.G.; Laupacis, A.; Gøtzsche, P.C.; Krleža-Jerić, K.; Hróbjartsson, A.; Mann, H.; Dickersin, K.; Berlin, J.A.; et al. SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials. Ann. Intern. Med. 2013, 158, 200. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McAlindon, T.E.; Driban, J.B.; Henrotin, Y.; Hunter, D.J.; Jiang, G.-L.; Skou, S.T.; Wang, S.; Schnitzer, T. OARSI Clinical Trials Recommendations: Design, conduct, and reporting of clinical trials for knee osteoarthritis. Osteoarthr. Cartil. 2015, 23, 747–760. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- The Royal Australian College of General Practitioners. Guideline for the Management of Knee and Hip Osteoarthritis, 2nd ed.; Victorian Coastal Council: East Melbourne, VIC, Australia, 2018; ISBN 978-0-86906-500-6. [Google Scholar]
- Hunter, D.J.; Bierma-Zeinstra, S. Osteoarthritis. Lancet 2019, 393, 1745–1759. [Google Scholar] [CrossRef] [PubMed]
- Faul, F.; Erdfelder, E.; Lang, A.-G.; Buchner, A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods 2007, 39, 175–191. [Google Scholar] [CrossRef]
- Tubach, F. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: The minimal clinically important improvement. Ann. Rheum. Dis. 2005, 64, 29–33. [Google Scholar] [CrossRef]
- Hawker, G.A.; Mian, S.; Kendzerska, T.; French, M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF). Arthritis Care Res. 2011, 63 (Suppl. 1), S240–S252. [Google Scholar] [CrossRef]
- Mehmet, H.; Robinson, S.R.; Yang, A.W.H. Assessment of Gait Speed in Older Adults. J. Geriatr. Phys. Ther. 2020, 43, 42–52. [Google Scholar] [CrossRef]
- Treede, R.-D.; Rief, W.; Barke, A.; Aziz, Q.; Bennett, M.I.; Benoliel, R.; Cohen, M.; Evers, S.; Finnerup, N.B.; First, M.B.; et al. Chronic pain as a symptom or a disease: The IASP classification of chronic pain for the International Classification of Diseases (ICD-11). Pain 2019, 160, 19–27. [Google Scholar] [CrossRef] [Green Version]
- Bascour-Sandoval, C.; Albayay, J.; Martínez-Molina, A.; Opazo-Sepúlveda, A.; Lacoste-Abarzúa, C.; Bielefeldt-Astudillo, D.; Gajardo-Burgos, R.; Galvéz-García, G. Psychometric Properties of the PCS and the PCS-4 in Individuals With Musculoskeletal Pain. Psicothema 2022, 34, 323–331. [Google Scholar] [CrossRef]
- Bretherton, B.; Atkinson, L.; Murray, A.; Clancy, J.; Deuchars, S.; Deuchars, J. Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: Potential benefits of daily stimulation. Aging 2019, 11, 4836–4857. [Google Scholar] [CrossRef]
- Colzato, L.S.; Wolters, G.; Peifer, C. Transcutaneous vagus nerve stimulation (tVNS) modulates flow experience. Exp. brain Res. 2018, 236, 253–257. [Google Scholar] [CrossRef] [Green Version]
- Nemeroff, C.B.; Mayberg, H.S.; Krahl, S.E.; McNamara, J.; Frazer, A.; Henry, T.R.; George, M.S.; Charney, D.S.; Brannan, S.K. VNS therapy in treatment-resistant depression: Clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 2006, 31, 1345–1355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Redgrave, J.; Day, D.; Leung, H.; Laud, P.J.; Ali, A.; Lindert, R.; Majid, A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018, 11, 1225–1238. [Google Scholar] [CrossRef]
- Colzato, L.S.; Ritter, S.M.; Steenbergen, L. Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking. Neuropsychologia 2018, 111, 72–76. [Google Scholar] [CrossRef] [PubMed]
- Kraus, T.; Kiess, O.; Hösl, K.; Terekhin, P.; Kornhuber, J.; Forster, C. CNS BOLD fMRI Effects of Sham-Controlled Transcutaneous Electrical Nerve Stimulation in the Left Outer Auditory Canal—A Pilot Study. Brain Stimul. 2013, 6, 798–804. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Moskowitz, R.W.; Nuki, G.; Abramson, S.; Altman, R.D.; Arden, N.; Bierma-Zeinstra, S.; Brandt, K.D.; Croft, P.; Doherty, M.; et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr. Cartil. 2008, 16, 137–162. [Google Scholar] [CrossRef] [Green Version]
- Pisters, M.F.; Veenhof, C.; van Meeteren, N.L.U.; Ostelo, R.W.; de Bakker, D.H.; Schellevis, F.G.; Dekker, J. Long-Term effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: A systematic review. Arthritis Rheum. 2007, 57, 1245–1253. [Google Scholar] [CrossRef]
- Bannuru, R.R.; Osani, M.C.; Vaysbrot, E.E.; Arden, N.K.; Bennell, K.; Bierma-Zeinstra, S.M.A.; Kraus, V.B.; Lohmander, L.S.; Abbott, J.H.; Bhandari, M.; et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr. Cartil. 2019, 27, 1578–1589. [Google Scholar] [CrossRef] [Green Version]
- Kolasinski, S.L.; Neogi, T.; Hochberg, M.C.; Oatis, C.; Guyatt, G.; Block, J.; Callahan, L.; Copenhaver, C.; Dodge, C.; Felson, D.; et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res. 2020, 72, 149–162. [Google Scholar] [CrossRef]
- Dworkin, R.H.; Evans, S.R.; Mbowe, O.; McDermott, M.P. Essential statistical principles of clinical trials of pain treatments. Pain Rep. 2021, 6, e863. [Google Scholar] [CrossRef]
- Tubach, F.; Ravaud, P.; Martin-Mola, E.; Awada, H.; Bellamy, N.; Bombardier, C.; Felson, D.T.; Hajjaj-Hassouni, N.; Hochberg, M.; Logeart, I.; et al. Minimum clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: Results from a prospective multina. Arthritis Care Res. 2012, 64, 1699–1707. [Google Scholar] [CrossRef] [PubMed]
- Katz, J.N.; Arant, K.R.; Loeser, R.F. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA 2021, 325, 568–578. [Google Scholar] [CrossRef] [PubMed]
Study Period | ||||||
---|---|---|---|---|---|---|
Activity | Recruitment and Assignment | Post-Assignment Stage | End of the Intervention | Follow-Up Stage | ||
Moment | −t1 | 0 | Month 1 | Month 2 | Month 4 | |
RECRUITMENT | ||||||
Screening | X | |||||
Informed Consent | X | |||||
Assignment | X | |||||
INTERVENTION | ||||||
Experimental group | X | |||||
Control group | X | |||||
EVALUATIONS | ||||||
Descriptive data | X | |||||
Primary variable | X | X | X | X | ||
Secondary variables | X | X | X | X | ||
Other variables | X |
Inclusion Criteria | Exclusion Criteria |
---|---|
|
|
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bascour-Sandoval, C.; Gajardo-Burgos, R.; Muñoz-Poblete, C.; Riedemann-González, P.; Erices-Salas, S.; Martínez-Molina, A.; Gálvez-García, G. Transcutaneous Vagal Stimulation in Knee Osteoarthritis (TRAVKO): Protocol of a Superiority, Outcome Assessor- and Participant-Blind, Randomised Controlled Trial. Int. J. Environ. Res. Public Health 2023, 20, 311. https://doi.org/10.3390/ijerph20010311
Bascour-Sandoval C, Gajardo-Burgos R, Muñoz-Poblete C, Riedemann-González P, Erices-Salas S, Martínez-Molina A, Gálvez-García G. Transcutaneous Vagal Stimulation in Knee Osteoarthritis (TRAVKO): Protocol of a Superiority, Outcome Assessor- and Participant-Blind, Randomised Controlled Trial. International Journal of Environmental Research and Public Health. 2023; 20(1):311. https://doi.org/10.3390/ijerph20010311
Chicago/Turabian StyleBascour-Sandoval, Claudio, Rubén Gajardo-Burgos, Claudio Muñoz-Poblete, Pablo Riedemann-González, Stephanie Erices-Salas, Agustín Martínez-Molina, and Germán Gálvez-García. 2023. "Transcutaneous Vagal Stimulation in Knee Osteoarthritis (TRAVKO): Protocol of a Superiority, Outcome Assessor- and Participant-Blind, Randomised Controlled Trial" International Journal of Environmental Research and Public Health 20, no. 1: 311. https://doi.org/10.3390/ijerph20010311