Clinical trial NCT04833660: rTMS on Diabetic Peripheral Neuropathic Pain
Official title: The Effect of Repetitive Transcranial Magnetic Stimulation on Diabetic Peripheral Neuropathic Pain: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Peripheral Neuropathic Pain
Keywords: diabetic peripheral neuropathy
diabetes
repetitive transcranial magnetic stimulation
pain
quality of life
Lead sponsor: Yeungnam University College of Medicine
Sponsor class: OTHER
First posted: 2021-04-06
Enrollment: 22
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Approximately half of the patients with long-standing diabetes are known to have diabetic peripheral neuropathy (DPN). Pain from DPN deteriorates the quality of life and hinders daily life activities.

Objectives: This study aimed to evaluate the effect of high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) on the left primary motor cortex (M1) for neuropathic pain in the lower extremities due to DPN.

Methods: In this randomized trial, 22 patients with DPN will randomly assign to the rTMS group (10 Hz stimulation, five sessions) or the sham group. A numeric rating scale (NRS) will use to measure pain intensity before treatment and after 1 day and 1 week of the treatment. Physical and mental health status will evaluate using the Short Form 36-Item Health Survey (SF-36), comprising two subscales (physical and mental component scores \[PCSs and MCSs\]), at 1-week post-treatment.


Eligibility criteria: Inclusion Criteria:

* diabetes
* neuropathic pain (stocking glove distribution) of a numeric rating scale (NRS) score of ≥3 (where 0 indicates no pain and 10 indicates the most intense pain imaginable) in the lower extremities
* pain duration of ≥3 months
* age between 21 and 80 years

Exclusion Criteria:

* presence of contraindications for TMS, such as a history of epileptic seizure, presence of metal in the skull, and presence of a cardiac pacemaker.

Primary outcomes:
measure: Pain before intervention to be assessed with Numeric Rating Scale
timeFrame: The NRS score will be assessed the day before starting the stimulation sessions (pre-treatment).
measure: Pain after intervention to be assessed with Numeric Rating Scale
timeFrame: The NRS score will be assessed 1 day after the completion of the sessions.
measure: Pain after intervention to be assessed with Numeric Rating Scale
timeFrame: The NRS score will be assessed 1 week after the completion of the sessions.
measure: Quality of life before intervention to be assessed with Short Form 36-Item Health Survey
timeFrame: The SF-36 PCS and SF-36 MCS will be measured the day before starting the stimulation sessions.
measure: Quality of life after intervention to be assessed with Short Form 36-Item Health Survey
timeFrame: The SF-36 PCS and SF-36 MCS will be measured 1 week after the completion of the sessions.
Secondary outcomes:
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
Study officials:
affiliation: Yuengnam University
name: Min Cheol Chang
role: STUDY_DIRECTOR
References:
citation: Dobretsov M, Romanovsky D, Stimers JR. Early diabetic neuropathy: triggers and mechanisms. World J Gastroenterol. 2007 Jan 14;13(2):175-91. doi: 10.3748/wjg.v13.i2.175.
citation: Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136-154. doi: 10.2337/dc16-2042. No abstract available.
citation: Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, Bril V, Russell JW, Viswanathan V. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun 13;5(1):41. doi: 10.1038/s41572-019-0092-1.
citation: Juster-Switlyk K, Smith AG. Updates in diabetic peripheral neuropathy. F1000Res. 2016 Apr 25;5:F1000 Faculty Rev-738. doi: 10.12688/f1000research.7898.1. eCollection 2016.
citation: Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008 Nov;88(11):1254-64. doi: 10.2522/ptj.20080020. Epub 2008 Sep 18.
citation: Schreiber AK, Nones CF, Reis RC, Chichorro JG, Cunha JM. Diabetic neuropathic pain: Physiopathology and treatment. World J Diabetes. 2015 Apr 15;6(3):432-44. doi: 10.4239/wjd.v6.i3.432.
citation: Yang S, Chang MC. Chronic Pain: Structural and Functional Changes in Brain Structures and Associated Negative Affective States. Int J Mol Sci. 2019 Jun 26;20(13):3130. doi: 10.3390/ijms20133130.
citation: Cohen K, Shinkazh N, Frank J, Israel I, Fellner C. Pharmacological treatment of diabetic peripheral neuropathy. P T. 2015 Jun;40(6):372-88.
citation: Chang MC. Conservative Treatments Frequently Used for Chronic Pain Patients in Clinical Practice: A Literature Review. Cureus. 2020 Aug 22;12(8):e9934. doi: 10.7759/cureus.9934.
citation: Choi GS, Kwak SG, Lee HD, Chang MC. Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study. J Rehabil Med. 2018 Feb 28;50(3):246-252. doi: 10.2340/16501977-2321.
citation: Gu SY, Chang MC. The Effects of 10-Hz Repetitive Transcranial Magnetic Stimulation on Depression in Chronic Stroke Patients. Brain Stimul. 2017 Mar-Apr;10(2):270-274. doi: 10.1016/j.brs.2016.10.010. Epub 2016 Oct 18.
citation: Ansari AH, Pal A, Ramamurthy A, Kabat M, Jain S, Kumar S. Fibromyalgia Pain and Depression: An Update on the Role of Repetitive Transcranial Magnetic Stimulation. ACS Chem Neurosci. 2021 Jan 20;12(2):256-270. doi: 10.1021/acschemneuro.0c00785. Epub 2021 Jan 4.
citation: Bursali C, Ozkan FU, Kaysin MY, Dortcan N, Aktas I, Kulcu DG. Effectiveness of Repetitive Transcranial Magnetic Stimulation in Patients With Failed Back Surgery Syndrome: A Double-Blind Randomized Placebo-Controlled Study. Pain Physician. 2021 Jan;24(1):E23-E30.
citation: Choi GS, Chang MC. Effects of high-frequency repetitive transcranial magnetic stimulation on reducing hemiplegic shoulder pain in patients with chronic stoke: a randomized controlled trial. Int J Neurosci. 2018 Feb;128(2):110-116. doi: 10.1080/00207454.2017.1367682. Epub 2017 Oct 2.
citation: Rodrigues PA, Zaninotto AL, Ventresca HM, Neville IS, Hayashi CY, Brunoni AR, de Paula Guirado VM, Teixeira MJ, Paiva WS. The Effects of Repetitive Transcranial Magnetic Stimulation on Anxiety in Patients With Moderate to Severe Traumatic Brain Injury: A Post-hoc Analysis of a Randomized Clinical Trial. Front Neurol. 2020 Dec 4;11:564940. doi: 10.3389/fneur.2020.564940. eCollection 2020.
citation: Onesti E, Gabriele M, Cambieri C, Ceccanti M, Raccah R, Di Stefano G, Biasiotta A, Truini A, Zangen A, Inghilleri M. H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy. Eur J Pain. 2013 Oct;17(9):1347-56. doi: 10.1002/j.1532-2149.2013.00320.x. Epub 2013 Apr 29.
citation: Ohn SH, Chang WH, Park CH, Kim ST, Lee JI, Pascual-Leone A, Kim YH. Neural correlates of the antinociceptive effects of repetitive transcranial magnetic stimulation on central pain after stroke. Neurorehabil Neural Repair. 2012 May;26(4):344-52. doi: 10.1177/1545968311423110. Epub 2011 Oct 6.
citation: 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.
citation: Ware JE, Kosinski M, Dewey JE. How to score version two of the SF-36 Health Survey. Lincoln, RI: QualityMetric Inc. 2001
citation: Hirayama A, Saitoh Y, Kishima H, Shimokawa T, Oshino S, Hirata M, Kato A, Yoshimine T. Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex. Pain. 2006 May;122(1-2):22-7. doi: 10.1016/j.pain.2005.12.001. Epub 2006 Feb 21.
citation: Yang S, Chang MC. Effect of Repetitive Transcranial Magnetic Stimulation on Pain Management: A Systematic Narrative Review. Front Neurol. 2020 Feb 18;11:114. doi: 10.3389/fneur.2020.00114. eCollection 2020.
citation: Almeida TF, Roizenblatt S, Tufik S. Afferent pain pathways: a neuroanatomical review. Brain Res. 2004 Mar 12;1000(1-2):40-56. doi: 10.1016/j.brainres.2003.10.073.
citation: Mylius V, Borckardt JJ, Lefaucheur JP. Noninvasive cortical modulation of experimental pain. Pain. 2012 Jul;153(7):1350-1363. doi: 10.1016/j.pain.2012.04.009. Epub 2012 May 26.
citation: Leung A, Donohue M, Xu R, Lee R, Lefaucheur JP, Khedr EM, Saitoh Y, Andre-Obadia N, Rollnik J, Wallace M, Chen R. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain. 2009 Dec;10(12):1205-16. doi: 10.1016/j.jpain.2009.03.010. Epub 2009 May 23.
citation: Garcia-Larrea L, Peyron R, Mertens P, Gregoire MC, Lavenne F, Le Bars D, Convers P, Mauguiere F, Sindou M, Laurent B. Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study. Pain. 1999 Nov;83(2):259-73. doi: 10.1016/s0304-3959(99)00114-1.
citation: Saitoh Y, Osaki Y, Nishimura H, Hirano S, Kato A, Hashikawa K, Hatazawa J, Yoshimine T. Increased regional cerebral blood flow in the contralateral thalamus after successful motor cortex stimulation in a patient with poststroke pain. J Neurosurg. 2004 May;100(5):935-9. doi: 10.3171/jns.2004.100.5.0935.
citation: Pagano RL, Fonoff ET, Dale CS, Ballester G, Teixeira MJ, Britto LRG. Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: possible pathways for antinociception. Pain. 2012 Dec;153(12):2359-2369. doi: 10.1016/j.pain.2012.08.002. Epub 2012 Sep 25.
citation: Attal N, Ayache SS, Ciampi De Andrade D, Mhalla A, Baudic S, Jazat F, Ahdab R, Neves DO, Sorel M, Lefaucheur JP, Bouhassira D. Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study. Pain. 2016 Jun;157(6):1224-1231. doi: 10.1097/j.pain.0000000000000510.
citation: Bertolucci F, Fanciullacci C, Rossi B, Chisari C. rTMS in the management of allodynia from brachial plexus injuries. Brain Stimul. 2013 Mar;6(2):218-9. doi: 10.1016/j.brs.2012.03.016. Epub 2012 Apr 12. No abstract available.
citation: Malavera A, Silva FA, Fregni F, Carrillo S, Garcia RG. Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial. J Pain. 2016 Aug;17(8):911-8. doi: 10.1016/j.jpain.2016.05.003. Epub 2016 May 31.
citation: Gaertner M, Kong JT, Scherrer KH, Foote A, Mackey S, Johnson KA. Advancing Transcranial Magnetic Stimulation Methods for Complex Regional Pain Syndrome: An Open-Label Study of Paired Theta Burst and High-Frequency Stimulation. Neuromodulation. 2018 Jun;21(4):409-416. doi: 10.1111/ner.12760. Epub 2018 Mar 4.
citation: Umezaki Y, Badran BW, DeVries WH, Moss J, Gonzales T, George MS. The Efficacy of Daily Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) for Burning Mouth Syndrome (BMS): A Randomized Controlled Single-blind Study. Brain Stimul. 2016 Mar-Apr;9(2):234-42. doi: 10.1016/j.brs.2015.10.005. Epub 2015 Oct 26.
citation: Yang S, Kwak SG, Choi GS, Chang MC. Short-term Effect of Repetitive Transcranial Magnetic Stimulation on Diabetic Peripheral Neuropathic Pain. Pain Physician. 2022 Mar;25(2):E203-E209.