rTMS on Diabetic Peripheral Neuropathic Pain

NCT04833660 | Unknown

• 1 other identifier: YUMC 2021-03-043
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Peripheral Neuropathic Pain

Keywords

diabetic peripheral neuropathy; diabetes; repetitive transcranial magnetic stimulation; pain; quality of life

Outcome Measures

Primary Outcomes (5)

• Pain before intervention to be assessed with Numeric Rating Scale

  We will be assessed pain intensity using the NRS score as the primary outcome. Average pain intensity during the 24 hours before NRS assessment will be investigated. The Numeric Rating Scale (NRS) is the simplest and most commonly used numeric scale in which people rate the pain from 0 (no pain) to 10 (worst pain).

  The NRS score will be assessed the day before starting the stimulation sessions (pre-treatment).

• Pain after intervention to be assessed with Numeric Rating Scale

  We will be assessed pain intensity using the NRS score as the primary outcome. Average pain intensity during the 24 hours before NRS assessment will be investigated. The Numeric Rating Scale (NRS) is the simplest and most commonly used numeric scale in which people rate the pain from 0 (no pain) to 10 (worst pain).

  The NRS score will be assessed 1 day after the completion of the sessions.

• Pain after intervention to be assessed with Numeric Rating Scale

  We will be assessed pain intensity using the NRS score as the primary outcome. Average pain intensity during the 24 hours before NRS assessment will be investigated. The Numeric Rating Scale (NRS) is the simplest and most commonly used numeric scale in which people rate the pain from 0 (no pain) to 10 (worst pain).

  The NRS score will be assessed 1 week after the completion of the sessions.

• Quality of life before intervention to be assessed with Short Form 36-Item Health Survey

  We will be measured health-related quality of life using the Short Form 36-Item Health Survey (SF-36). The SF-36 has two subscales: physical component score (PCS) and mental component score (MCS), reflecting overall physical and mental health status, respectively. The SF-36 consists of eight components: physical functioning, physical role functioning, bodily pain, general health perceptions, vitality, social role functioning, emotional role functioning, and mental health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

  The SF-36 PCS and SF-36 MCS will be measured the day before starting the stimulation sessions.

• Quality of life after intervention to be assessed with Short Form 36-Item Health Survey

  We will be measured health-related quality of life using the Short Form 36-Item Health Survey (SF-36). The SF-36 has two subscales: physical component score (PCS) and mental component score (MCS), reflecting overall physical and mental health status, respectively. The SF-36 consists of eight components: physical functioning, physical role functioning, bodily pain, general health perceptions, vitality, social role functioning, emotional role functioning, and mental health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

  The SF-36 PCS and SF-36 MCS will be measured 1 week after the completion of the sessions.

Study Arms (2)

rTMS group

EXPERIMENTAL

Each patient will receive five consecutive sessions (Monday to Friday for 1 week). Patients in the rTMS group will administer rTMS over the optimal scalp site at 10 Hz, with an intensity of 90% of the MT and a duration of 5 seconds, for a total of 20 trains separated by 55-second intertrain pauses (a total of 1,000 pulses). The coil will be placed tangentially to the scalp at an approximate angle of 45° tilted backward and laterally. Oral medication dosages of all patients will unchanged during the stimulation and follow-up periods.

Device: repetitive transcranial magnetic stimulation

sham group

SHAM COMPARATOR

Patients in the sham group will administer sham stimulation using the same protocol, except that the angle of the coil is 90° (i.e., perpendicular, rather than tangential) to the skull. Oral medication dosages of all patients will unchanged during the stimulation and follow-up periods.

Device: repetitive transcranial magnetic stimulation

Interventions

repetitive transcranial magnetic stimulation DEVICE

Repetitive transcranial magnetic stimulation (rTMS) is a safe, noninvasive, and effective therapeutic intervention that uses an electromagnetic coil applied to the scalp to produce a magnetic field. rTMS induces changes in cortical excitability at the stimulation site and transsynaptically at distant areas. Cortical excitability is increased by high-frequency (≥5 Hz) stimulation and is decreased by low-frequency (1 Hz) stimulation. The application of high-frequency unilateral rTMS to the motor cortex in patients is reported to have a potential to control various types of pain, such as neuropathic pain, fibromyalgia, and musculoskeletal origin pain (myofascial pain syndrome, shoulder pain, and lower back pain).

rTMS group; sham group

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Min Cheol Chang: lead

Study Sites (1)

Yeungnam University Hospital

Daegu, 705-717, South Korea

Location

Related Publications (33)

• 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.

  PMID: 17226897 BACKGROUND

• 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.

  PMID: 27999003 BACKGROUND

• 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.

  PMID: 31197153 BACKGROUND

• 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.

  PMID: 27158461 BACKGROUND

• 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.

  PMID: 18801858 BACKGROUND

• 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.

  PMID: 25897354 BACKGROUND

• 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.

  PMID: 31248061 BACKGROUND

• Cohen K, Shinkazh N, Frank J, Israel I, Fellner C. Pharmacological treatment of diabetic peripheral neuropathy. P T. 2015 Jun;40(6):372-88.

  PMID: 26045647 BACKGROUND

• 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.

  PMID: 32968595 BACKGROUND

• 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.

  PMID: 29392332 BACKGROUND

• 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.

  PMID: 27839722 BACKGROUND

• 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.

  PMID: 33397091 BACKGROUND

• 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.

  PMID: 33400434 BACKGROUND

• 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.

  PMID: 28805107 BACKGROUND

• 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.

  PMID: 33343483 BACKGROUND

• 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.

  PMID: 23629867 BACKGROUND

• 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.

  PMID: 21980153 BACKGROUND

• 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 BACKGROUND

• Ware JE, Kosinski M, Dewey JE. How to score version two of the SF-36 Health Survey. Lincoln, RI: QualityMetric Inc. 2001

  BACKGROUND

• 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.

  PMID: 16495011 BACKGROUND

• 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.

  PMID: 32132973 BACKGROUND

• 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.

  PMID: 15053950 BACKGROUND

• 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.

  PMID: 22633979 BACKGROUND

• 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.

  PMID: 19464959 BACKGROUND

• 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.

  PMID: 10534598 BACKGROUND

• 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.

  PMID: 15137612 BACKGROUND

• 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.

  PMID: 23017297 BACKGROUND

• 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.

  PMID: 26845524 BACKGROUND

• 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.

  PMID: 22521080 BACKGROUND

• 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.

  PMID: 27260638 BACKGROUND

• 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.

  PMID: 29504190 BACKGROUND

• 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.

  PMID: 26597930 BACKGROUND

• 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.

  PMID: 35322973 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Pain

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Min Cheol Chang

  Yuengnam University

  STUDY DIRECTOR

Central Study Contacts

Chang

CONTACT

+82-10-9362-1220; wheel633@ynu.ac.kr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: April 6, 2021
• Study Start: April 30, 2021
• Primary Completion: May 25, 2021
• Study Completion: June 15, 2021
• Last Updated: April 22, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)