Repetitive Transcranial Magnetic Stimulation (rTMS) in Fibromyalgia

Fibromyalgia Clinical Trial

Official title:

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Pain, Fatigue, Quality of Life, Cognitive Function and Mood in Fibromyalgia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03909009
• Other study ID #: 14032019
• Status: Completed
• Phase: N/A
• Start date: April 11, 2019
• Est. completion date: April 10, 2020

Study information

• Verified date: June 2020
• Source: Izmir Katip Celebi University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the effectiveness of 10 Hz neuronavigated repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) on pain, stiffness, fatigue, depression/anxiety, quality of life and cognitive functions in fibromyalgia syndrome (FMS).

Description:

This is a single-center, prospective, randomized, double-blind, sham-controlled study in two-arm parallel-group design. Twenty participants will be randomized into 2 groups. Randomization will be performed using computer-generated block randomization with 1:1 allocation between the active rTMS group (Group 1) and the sham-control group (Group 2). Group 1 will receive high frequency repetitive transcranial magnetic stimulation (10hz-HF-rTMS)-A total 14 sessions of HF-rTMS, 10 sessions daily (5 days/week, 2 weeks) and 4 sessions weekly (1 day/week, 4 weeks). Group 2 will receive sham stimulation-A total 14 sessions of sham-rTMS, 10 sessions daily (5 days/week, 2 weeks) and 4 sessions weekly (1 day/week, 4 weeks).All patients will be evaluated with pain severity (VAS-10mm),stiffness severity (VAS-10mm), Fibromyalgia Impact Questionnaire (FIQ), Fatigue Severity Scale (FSS), Hospital Depression Anxiety Scale (HADS), Addenbrook Cognitive Examination-revised version (ACE-R).Patients will be questioned for the safety of treatment. Available drug therapies will be continued in both groups. Patients and clinical raters will be blinded to treatment. All patients will be reviewed by the investigator in terms of rTMS treatment safety and motor threshold determination before each treatment session and observed for possible side effects after treatment. All side effects will be recorded. Magnetic stimulation will be applied using Neurosoft-Neuro MS/D with a figure-of-eight-shaped coil. rTMS therapy will be applied under the guide of neuronavigation with the following parameters: target-left DLPFC, with the %90 of the RMT, 10 Hz stimulation for 5 seconds intervals (on) with 25 seconds inter-train intervals (off), 15 minutes, 1500 pulses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 10, 2020
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adults (age between 18-65 years)

• Diagnosis of fibromyalgia syndrome according to 2016 Fibromyalgia diagnostic criteria

• The mean pain intensity is VAS = 4/10

• Stable treatment for at least last 3 months

• Patients accepting participation by signing an informed consent form

Exclusion Criteria:

• To have a clinical condition to be contraindicated for TMS (metallic implant, cardiac pace, pregnancy, lactation, epilepsy, head trauma, history of cranial operation...)

• The presence of malignancy

• Systemic rheumatic diseases

• Major orthopedic / neurological problems that limit daily life activities

• Alcohol or drug addiction

• Major depression / personality disorder history

• Have received TMS treatment before

• Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

Intervention

Device:
• rTMS + Neuronavigation
Repetitive Transcranial Magnetic Stimulation (Neuro-MS/D) + Neural Navigator

Locations

Country	Name	City	State
Turkey	Izmir Katip Çelebi University Faculty of Medicine, Department of Physical Medicine and Rehabilitation	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
Izmir Katip Celebi University

Country where clinical trial is conducted

Turkey, 

References & Publications (10)

Baudic S, Attal N, Mhalla A, Ciampi de Andrade D, Perrot S, Bouhassira D. Unilateral repetitive transcranial magnetic stimulation of the motor cortex does not affect cognition in patients with fibromyalgia. J Psychiatr Res. 2013 Jan;47(1):72-7. doi: 10.1016/j.jpsychires.2012.09.003. Epub 2012 Oct 15. — View Citation

Hou WH, Wang TY, Kang JH. The effects of add-on non-invasive brain stimulation in fibromyalgia: a meta-analysis and meta-regression of randomized controlled trials. Rheumatology (Oxford). 2016 Aug;55(8):1507-17. doi: 10.1093/rheumatology/kew205. Epub 2016 May 5. Review. — View Citation

Klein MM, Treister R, Raij T, Pascual-Leone A, Park L, Nurmikko T, Lenz F, Lefaucheur JP, Lang M, Hallett M, Fox M, Cudkowicz M, Costello A, Carr DB, Ayache SS, Oaklander AL. Transcranial magnetic stimulation of the brain: guidelines for pain treatment research. Pain. 2015 Sep;156(9):1601-14. doi: 10.1097/j.pain.0000000000000210. Review. — View Citation

Knijnik LM, Dussán-Sarria JA, Rozisky JR, Torres IL, Brunoni AR, Fregni F, Caumo W. Repetitive Transcranial Magnetic Stimulation for Fibromyalgia: Systematic Review and Meta-Analysis. Pain Pract. 2016 Mar;16(3):294-304. doi: 10.1111/papr.12276. Epub 2015 Jan 12. Review. — View Citation

Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jääskeläinen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorová I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1. Review. Erratum in: Clin Neurophysiol. 2020 May;131(5):1168-1169. — View Citation

Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5. Review. — View Citation

Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14. Review. — View Citation

Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10. Review. — View Citation

Saltychev M, Laimi K. Effectiveness of repetitive transcranial magnetic stimulation in patients with fibromyalgia: a meta-analysis. Int J Rehabil Res. 2017 Mar;40(1):11-18. doi: 10.1097/MRR.0000000000000207. Review. — View Citation

Tekin A, Özdil E, Güleken MD, Iliser R, Bakim B, Öncü J, et al. Efficacy of HighFrequency [10 Hz] Repetitive Transcranial Magnetic Stimulation of the PrimaryMotor Cortex in Patients with Fibromyalgia Syndrome: A Randomized, DoubleBlind, Sham-Controlled Trial. Journal of Musculoskeletal Pain. 2014;22(1):20-26.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Visual Analog Scale-Stiffness	The severity of the stiffness at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no stiffness, 10=severe stiffness) Higher scores mean a worse outcome.	in the second week
Other	Fibromyalgia Impact Questionnaire	Functional health status and quality of life of the participants were assessed with the Fibromyalgia impact questionnaire, which measures 10 different features (physical functioning, missed days of work, depression, anxiety, feeling good, morning tiredness, pain, stiffness, fatigue, and well-being over the past week). The total Fibromyalgia impact questionnaire score is maximum 80 points. Higher scores indicate lower functionality level.	in the second week
Other	Fatigue Severity Scale	Severity of fatigue was evaluated with Fatigue severity scale, a 9-item self-report questionnaire scale. Each item of this scale consists of statements that are scored on a seven-point Likert type scale ranging from 1 to 7. Total Fatigue severity scale score is calculated as the mean value of nine items. Higher scores indicate higher fatigue severity. (Total score range: 1-7)	in the sixth week
Other	Hospital Anxiety and Depression Scale	Hospital anxiety and depression scale is an assessment tool developed to identify the risk of anxiety and depression and measure its level and change of severity. Its subscales are anxiety and depression. It contains 14 questions in total, including 7 (odd numbers) measuring anxiety and 7 (even numbers) measuring depression. The lowest and highest total score that a person can obtain from this scale are 0 and 42, respectively. High scores are associated with a worse psychiatric condition.	in the sixth week
Other	Addenbrook Cognitive Examination Revised	Addenbrook Cognitive Examination-Revised is a brief cognitive test that consists of 5 basic sections: attention and orientation, memory, verbal fluency, language and visual-spatial abilities. Total score that can be obtained is 0-100. Higher scores are associated with a better cognitive state.	in the sixth week
Primary	Visual Analog Scale-Pain	The severity of the pain at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no pain, 10=severe pain) Higher scores mean a worse outcome.	in the second week
Secondary	Visual Analog Scale-Pain	The severity of the pain at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no pain, 10=severe pain) Higher scores mean a worse outcome.	in the sixth week
Secondary	Fibromyalgia Impact Questionnaire	Functional health status and quality of life of the participants were assessed with the Fibromyalgia impact questionnaire, which measures 10 different features (physical functioning, missed days of work, depression, anxiety, feeling good, morning tiredness, pain, stiffness, fatigue, and well-being over the past week). The total Fibromyalgia impact questionnaire score is maximum 80 points. Higher scores indicate lower functionality level.	in the sixth week