A Study Comparing Real and Sham Repetitive Transcranial Magnetic Stimulation in Adults With Fibromyalgia, Assessing Effects on Pain, Fatigue, Sleep, Mood, Quality of Life, Cognition, and Walking Under Usual and Dual-task Conditions (FMS-TMS-GAIT)

The Effect of Repetitive Transcranial Magnetic Stimulation on Symptoms and Gait in Patients With Primary Fibromyalgia

Fibromyalgia is a chronic condition that causes widespread pain and is often accompanied by fatigue, poor sleep, mood symptoms, memory and concentration difficulties, and reduced quality of life. Many adults with fibromyalgia also experience limitations in daily physical functioning. These limitations may include slower or less stable walking, reduced walking endurance, and greater difficulty walking while performing another task at the same time, such as counting or carrying out a mental task.

This clinical study is designed to evaluate the effects of repetitive transcranial magnetic stimulation, also called rTMS, in adults with fibromyalgia. rTMS is a non-invasive brain stimulation technique that delivers magnetic pulses through the scalp to influence activity in specific brain areas involved in pain processing, mood regulation, and physical function. The procedure does not require surgery or anesthesia.

Participants in this study are randomly assigned to receive either real rTMS or sham rTMS. Sham rTMS is designed to look and feel similar to the real procedure but does not deliver active therapeutic brain stimulation. Comparing real and sham rTMS allows researchers to assess whether any observed improvements are related to the active treatment rather than to expectation or participation in the study.

The study evaluates whether real rTMS can improve symptoms and function in adults with fibromyalgia. Outcomes include pain, fatigue, mood, sleep, quality of life, cognition, and walking performance. Walking is assessed during usual walking and during dual-task walking, when participants walk while also performing another task. These assessments are used to better understand how fibromyalgia affects everyday functioning and whether rTMS may help improve both symptoms and objective physical performance.

The main hypothesis is that participants who receive real rTMS will show greater improvement than those who receive sham rTMS. It is expected that real rTMS may reduce pain and related symptoms, improve quality of life and cognitive or emotional functioning, and have a favorable effect on walking performance, especially under more demanding dual-task conditions.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia Syndrome
• Intervention / Treatment: Device: Active repetitive transcranial magnetic stimulation; Device: Sham repetitive transcranial magnetic stimulation

Detailed Description

Fibromyalgia is a chronic pain condition characterized by widespread pain, fatigue, sleep problems, difficulties with memory and concentration, mood symptoms, and reduced quality of life. In addition to these symptoms, many adults with fibromyalgia also experience problems with physical functioning, balance, and walking. Walking is not only a physical activity but also requires attention, planning, and coordination between the brain and body. These demands become even greater when a person walks while performing another task at the same time, such as counting, thinking, or carrying an object. This is called dual-task walking and may reflect challenges that occur in everyday life.

Current drug treatments for fibromyalgia often provide only limited symptom relief and may sometimes affect cognition, balance, or physical functioning. For this reason, non-drug approaches are important in the management of fibromyalgia. Repetitive transcranial magnetic stimulation, or rTMS, is a non-invasive brain stimulation technique that uses magnetic pulses delivered through a coil placed on the scalp. These pulses can influence the activity of brain areas involved in pain processing, mood, attention, cognition, and movement control. The procedure does not require surgery or anesthesia.

This study will investigate the effects of rTMS applied over the left dorsolateral prefrontal cortex, a brain region involved in pain modulation, mood regulation, executive function, attention, and cognitive control of walking. The study is designed to evaluate whether real rTMS can improve walking performance and clinical symptoms in adults with fibromyalgia when compared with sham rTMS.

This will be a single-center, randomized, double-blind, sham-controlled clinical study conducted in adults with primary fibromyalgia. Participants will be adults with fibromyalgia whose diagnosis is confirmed according to established classification criteria. Eligible participants have chronic pain lasting more than three months, pain of at least moderate intensity, and persistent symptoms despite conventional pharmacological treatment. Participants are required to be right-handed and able to understand and sign the informed consent form.

People with other conditions that could explain widespread pain or significantly affect walking, balance, cognition, or safety are not included. These include unstable chronic diseases, inflammatory or autoimmune rheumatic diseases, significant degenerative musculoskeletal conditions affecting gait or balance, major psychiatric disorders, neurological disorders causing motor or cognitive deficits, pregnancy or breastfeeding, active infection, malignancy, high fracture risk, and standard safety contraindications to rTMS such as epilepsy, pacemakers, certain implants, metal in the head, or medicines that substantially lower the seizure threshold.

Participants will be randomly assigned to receive either real rTMS or sham rTMS. Randomization will be performed using a computer-generated allocation sequence, and treatment allocation is concealed. Participants and outcome assessors will be blinded to the assigned treatment. Before randomization, participants will be stratified according to the presence or absence of depressive symptoms, because depression may influence both walking performance and response to rTMS.

In the real rTMS group, stimulation will be applied over the left dorsolateral prefrontal cortex. Before treatment, each participant's individual motor threshold will be determined using stimulation of the left primary motor cortex and recording responses from the contralateral hand muscle. The stimulation target will be then identified using a standard 5-cm method from the motor hotspot. The real rTMS protocol uses high-frequency stimulation at 10 Hz and an intensity based on the individual motor threshold. Each treatment session includes repeated stimulation trains and a total of 2,000 magnetic pulses per day. Participants will receive 10 daily sessions over two weeks, on working days, with a weekend break.

In the sham rTMS group, stimulation will be delivered using a sham coil placed over the same scalp region. Sham stimulation will be designed to look and sound similar to real rTMS but does not provide effective therapeutic brain stimulation. The number of sessions, session structure, stimulation schedule, and overall procedure are otherwise the same as in the real rTMS group. This comparison allows the study to evaluate whether any observed effects are due to active brain stimulation rather than expectation, attention from healthcare staff, or participation in the study.

The main outcome of the study will be the change in walking performance from before to after treatment, especially during dual-task walking. Walking will be measured using an electronic walkway system. Participants walk at their usual comfortable speed during simple walking and during different dual-task conditions. These include walking while carrying a glass of water, walking while performing a mental task, and walking while performing both the motor and mental tasks together. The walking assessment measures spatiotemporal gait parameters such as cycle time, stride length, swing time, double support time, and variability of these measures.

The study will also evaluate several clinical outcomes that are important to people with fibromyalgia. These include pain intensity, pain severity and pain interference with daily activities, depressive symptoms, anxiety symptoms, sleep quality and sleep-related problems, fatigue, health-related quality of life, cognitive function, and overall fibromyalgia impact. These outcomes will be assessed using validated questionnaires and clinical instruments before and after the treatment period.

The main hypothesis is that adults with fibromyalgia who receive real rTMS will show greater improvement than those who receive sham rTMS. The study expects that real rTMS may improve walking performance, particularly during more demanding dual-task walking, and may also reduce pain, fatigue, mood symptoms, sleep problems, cognitive difficulties, and overall fibromyalgia-related burden.

Safety will be monitored throughout the treatment period. Participants will be asked about possible adverse effects, including scalp or site discomfort, headache, neck pain, nausea, dizziness, or other symptoms. Serious adverse events will be also monitored, although serious complications from rTMS are rare when standard safety procedures are followed.

By combining objective walking assessment with patient-reported outcomes, this study aims to provide a more complete understanding of how rTMS may affect both symptoms and daily functioning in fibromyalgia. The findings may help clarify whether stimulation of the left dorsolateral prefrontal cortex could be a useful additional non-drug treatment approach for adults with fibromyalgia, particularly for symptoms and functional limitations that affect everyday life.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of fibromyalgia based on the revised 2016 American College of Rheumatology criteria.
2. A Visual Analogue Scale pain score of at least 4, with pain present for more than 3 months before inclusion in the study.
3. Pain resistant to standard analgesics, including paracetamol, nonsteroidal anti-inflammatory drugs, and low-potency opioids, administered at full therapeutic doses.
4. If receiving treatment for fibromyalgia, participants had to be on a stable dose for more than 1 month before inclusion in the study.
5. No previous treatment with repetitive transcranial magnetic stimulation.

Exclusion Criteria:

1. Inability to provide informed consent.
2. Other chronic conditions, diseases, or disorders that may cause diffuse pain, such as endocrine or metabolic diseases.
3. Other degenerative, orthopedic, or surgical diseases of the musculoskeletal system that significantly affect gait, including the use of crutches or a walking cane.
4. Presence of a chronic inflammatory rheumatic disease.
5. Presence of a systemic autoimmune disease.
6. Primary psychiatric diagnosis, including previously diagnosed severe depressive disorder, generalized anxiety disorder, or psychosis.
7. Psychoactive substance abuse.
8. Neurological diseases that have caused or may cause cognitive or motor deficits.
9. Specific conditions such as active infections, malignancy, osteoporosis with high fracture risk, fractures, and similar conditions.
10. Contraindications to repetitive transcranial magnetic stimulation, including epilepsy, central nervous system trauma, brain surgery, intracranial hemorrhage, implanted pacemaker or other metal implant, pregnancy, or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active rTMS; Participants assigned to this arm will receive active repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex. Stimulation will be delivered at 10 Hz and 130% of the individually determined motor threshold. Each session will include 2,000 pulses, delivered as 40 trains of 50 pulses, with 5-second stimulation trains and 20-second inter-train intervals. Treatment will consist of 10 daily sessions over two weeks, administered on working days.	Device: Active repetitive transcranial magnetic stimulation; Active high-frequency repetitive transcranial magnetic stimulation delivered over the left dorsolateral prefrontal cortex using a figure-of-eight coil. Stimulation was delivered at 10 Hz and 130% of the individually determined motor threshold, with 2,000 pulses per session over 10 daily sessions during two weeks.; Other Names: Active rTMS
Sham Comparator: Sham rTMS; Participants assigned to this arm will receive sham repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex using a dedicated sham coil. Sham stimulation will reproduce the acoustic characteristics of active rTMS while preventing effective cortical stimulation. The stimulation parameters, number of pulses, train duration, inter-train interval, number of sessions, and treatment schedule were identical to the active rTMS arm.	Device: Sham repetitive transcranial magnetic stimulation; Sham repetitive transcranial magnetic stimulation delivered over the left dorsolateral prefrontal cortex using a dedicated sham coil. The sham coil reproduced the acoustic characteristics of active stimulation while preventing effective cortical stimulation. The session schedule and stimulation structure were identical to the active rTMS arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in dual-task gait parameters from baseline to post-treatment	The primary outcome is the between-group difference between active repetitive transcranial magnetic stimulation and sham stimulation in pre-post change in dual-task gait parameters. Gait was assessed using the GAITRite electronic walkway during dual-task walking conditions, including motor, mental, and combined motor-cognitive tasks. Spatiotemporal gait parameters included cycle time, stride length, swing time, double support time, and the coefficients of variation of these parameters. Changes were expressed as absolute delta values and relative percentage delta values from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain intensity from baseline to post-treatment	Pain intensity was assessed using the Visual Analogue Scale for pain. Scores are recorded on a 100-mm line, with higher scores indicating greater pain intensity. The outcome was evaluated as the change from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in pain severity and pain interference from baseline to post-treatment	Pain severity and pain interference with daily activities were assessed using the Brief Pain Inventory-Short Form. Higher scores indicate greater pain burden. The outcome was evaluated as the change from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in depressive symptoms from baseline to post-treatment	Depressive symptoms were assessed using the Beck Depression Inventory, a 21-item self-report questionnaire. Higher scores indicate greater depression severity. The outcome was evaluated as the change from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in anxiety symptoms from baseline to post-treatment	Anxiety symptoms were assessed using the Beck Anxiety Inventory. Higher scores indicate greater anxiety severity. The outcome was evaluated as the change from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in sleep quality and sleep-related problems from baseline to post-treatment	Sleep quality and sleep-related problems were assessed using the Medical Outcomes Study Sleep Scale. The scale evaluates sleep disturbance, snoring, awakening with shortness of breath or headache, sleep adequacy, sleep quantity, daytime sleepiness, Sleep Problems Index I, and Sleep Problems Index II. Higher scores on sleep disturbance, daytime sleepiness, and sleep problem indices indicate greater sleep impairment, whereas higher sleep adequacy scores indicate better perceived sleep adequacy.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in fatigue from baseline to post-treatment	Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire. Lower scores indicate greater fatigue severity. The outcome was evaluated as the change from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in health-related quality of life from baseline to post-treatment	Health-related quality of life was assessed using the 36-Item Short Form Health Survey. The questionnaire evaluates physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. Physical Component Summary and Mental Component Summary scores were also calculated. Higher scores indicate better perceived health status and quality of life.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in cognitive function from baseline to post-treatment	Cognitive function was assessed using the Montreal Cognitive Assessment. Lower scores indicate poorer cognitive performance. The outcome was evaluated as the change from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Change in fibromyalgia impact from baseline to post-treatment	Fibromyalgia-related disease impact and functional impairment were assessed using the Revised Fibromyalgia Impact Questionnaire. Higher scores indicate greater fibromyalgia severity and poorer quality of life. The outcome was evaluated as the change from baseline to post-treatment.	Baseline and immediately after completion of the 10-session treatment protocol, approximately 2 weeks.
Incidence of adverse events during treatment	Safety was assessed by recording adverse events during the treatment period. Reported adverse events were grouped into predefined categories, including site discomfort, headache, neck pain, nausea, dizziness, and other adverse events.	During the 10-session treatment protocol, approximately 2 weeks.

Collaborators and Investigators

• Sponsor: Institute of Rheumatology, Serbia
• Collaborators: University of Belgrade
• Investigators: Principal Investigator: Goran L Radunović, MD, PhD, Medical Faculty, University of Belgrade

Publications and helpful links

General Publications

• Yogev-Seligmann G, Hausdorff JM, Giladi N. The role of executive function and attention in gait. Mov Disord. 2008 Feb 15;23(3):329-42; quiz 472. doi: 10.1002/mds.21720.
• Carrasco-Vega E, Ruiz-Munoz M, Cuesta-Vargas A, Romero-Galisteo RP, Gonzalez-Sanchez M. Individuals with fibromyalgia have a different gait pattern and a reduced walk functional capacity: a systematic review with meta-analysis. PeerJ. 2022 Mar 21;10:e12908. doi: 10.7717/peerj.12908. eCollection 2022.
• Ceron-Lorente L, Valenza MC, Perez-Marmol JM, Garcia-Rios MDC, Castro-Sanchez AM, Aguilar-Ferrandiz ME. The influence of balance, physical disability, strength, mechanosensitivity and spinal mobility on physical activity at home, work and leisure time in women with fibromyalgia. Clin Biomech (Bristol). 2018 Dec;60:157-163. doi: 10.1016/j.clinbiomech.2018.10.009. Epub 2018 Oct 10.
• Goes SM, Leite N, Shay BL, Homann D, Stefanello JM, Rodacki AL. Functional capacity, muscle strength and falls in women with fibromyalgia. Clin Biomech (Bristol). 2012 Jul;27(6):578-83. doi: 10.1016/j.clinbiomech.2011.12.009. Epub 2012 Jan 9.
• Radunovic G, Velickovic Z, Rasic M, Janjic S, Markovic V, Radovanovic S. Assessment of gait in patients with fibromyalgia during motor and cognitive dual task walking: a cross-sectional study. Adv Rheumatol. 2021 Aug 26;61(1):53. doi: 10.1186/s42358-021-00212-5.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): March 30, 2025
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Fibromyalgia; Prefrontal Cortex; Gait Analysis; Patient Reported Outcome Measures
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Fibromyalgia
• Other Study ID Numbers: No 29/16 on 27.08.2021.

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results of this study will be made available upon reasonable request from the corresponding author. Data will be shared for scientifically justified research purposes after review and approval of the request.
• IPD Sharing Time Frame: De-identified individual participant data and supporting documents will become available after publication of the main study results. Data will be shared upon reasonable request to the corresponding author, after review and approval of the proposed research purpose.
• IPD Sharing Access Criteria: De-identified individual participant data and supporting documents will be shared with qualified researchers upon reasonable request to the corresponding author. Requests should include a scientifically justified research proposal, planned analyses, and a data protection plan. Data may be used for research purposes related to fibromyalgia, repetitive transcranial magnetic stimulation, gait, pain, mood, sleep, cognition, quality of life, or related clinical outcomes. Requests will be reviewed by the study investigators, and access will be granted after approval of the proposal and, where appropriate, completion of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No