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

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.

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.

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.