Investigating the Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on the Brain in People With Fibromyalgia

Official title

Investigating the Differential Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Left and Right Motor Cortex in Fibromyalgia: A Prospective Randomized Trial With Functional Magnetic Resonance Imaging (MRI(

Overview

The first goal of this study is to see how brain activity changes in people with fibromyalgia after they get a treatment called rTMS (repetitive transcranial magnetic stimulation). Researchers are looking at how the parts of the brain that control movement (called motor cortices) respond to this treatment. The second goal is to find out if the changes in brain activity are different between the right and left sides of the brain, depending on which side gets the treatment.

Detailed description

The first aim of this study is to measure changes in fibromyalgia-related functional brain plasticity, as indicated by the functional "connectopy" of the right and left primary motor cortices in response to rTMS treatment. The second aim of this study is to explore whether changes in motor cortex connectopy differ between the right and left motor cortex (M1) following rTMS administered to each respective hemisphere.

Interventions

• Other rTMS
  Using rTMS, which is a procedure that uses magnetic fields to stimulate nerve cells in the brain, to investigate its potential analgesic effects in fibromyalgia.

Primary outcome measures

• Mean Change in Primary Motor Cortex (M1) Connectopy Profile [Time frame: Baseline and post-treatment (after 10 sessions of rTMS over 2 weeks).]

Secondary outcome measures (12)

• Mean Change in Pain Intensity (Numeric Rating Scale, NRS) [Time frame: Baseline and post-treatment (following 10 rTMS sessions, within 7 days of completing rTMS sessions ).]
• Mean Change in Pressure Pain Threshold (PPT) [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions )]
• Mean Change in Fatigue (Patient-Reported Outcomes Measurement Information System-PROMIS Fatigue 13a Subscale) [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in Sleep Disturbance (Patient-Reported Outcomes Measurement Information System - PROMIS Sleep Disturbance 8a Subscale) [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in the Short-Form McGill Pain Questionnaire [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in Central Sensitization Index [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in Pain Catastrophizing Scale [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in the Pain Self-repot Survey for the Assessment of Fibromyalgia [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in Revised Fibromyalgia Impact Questionnaire [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in Pittsburgh Sleep Quality Index (PSQI) [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in Chronic Overlapping Pain Conditions Screener [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]
• Mean Change in Hospital Anxiety and Depression Scale [Time frame: Baseline and post-treatment (within 7 days of completing rTMS sessions).]

Eligibility criteria

Inclusion criteria

• Female aged 18 to 65, right-handed, with no racial/ethnic restrictions.
• A diagnosis of fibromyalgia by a qualified physician according to the American College of Rheumatology 2016 criteria
• Must have a history of fibromyalgia pain for a duration ≥ 3 months, as it is included in the diagnostic criteria.
• Must have pain intensity equal or greater than 4/10 on the numerical rating scale (NRS) at enrollment.
• Concurrent chronic overlapping pain conditions (except migraine with aura), depression, and anxiety will be allowed when mild to moderate (Less than 31 on Beck Depression Inventory or less than 36 on Beck Anxiety Inventory), except in cases with psychotic or manic features.
• Concomitant medication (except tricyclics, antipsychotic medications, bupropion, methadone, theophylline) and their doses for mood, pain and sleep disorders must be steady at least 4 weeks before enrolment and must be kept at a steady dosage during the trial.
• Must be able to read and speak English and be willing to read and understand instructions as well as questionnaires.
• Must be in generally stable health.
• Must sign an informed consent document after explanation of the study documenting that they understand the purpose of the study, procedures to be undertaken, possible benefits, potential risks, and are willing to participate.

Exclusion criteria

• Inability to provide informed consent.
• Age outside the studied range (i.e., < 18, > 65).
• Patients planning to change their medications during trial.
• Participants who are currently receiving other alternative therapies during trial (e.g., physiotherapy, acupuncture).
• History of receiving TMS, transcranial direct current stimulation (tDCS), or electroconvulsive therapy (ECT).
• Evidence of rheumatologic disorders, autoimmune diseases, taking immunosuppressive treatment, severe or unstable cardiac diseases.
• Fibromyalgia must be the primary complaint; hence patients cannot have another main source of pain (e.g., osteoarthritis). Patients will be asked to shade all the areas in which they experience pain on a body map. If they shade areas other than typical fibromyalgia pain, we will discuss any previous diagnosis, the intensity and chronicity of pain, and exclude them if chronic pain in any area outside the condition in to be studied is confirmed.
• Involvement in litigation regarding their pain or having a disability claim or receiving workman compensation or seeking either because of their pain.
• Any history of hemorrhagic or thrombotic stroke.
• History of schizophrenia, schizoaffective disorder, bipolar disorders, mania, hypomania, eating disorders, or any psychiatric illness with psychotic features (major depressive disorder, mild to moderate without psychosis, or anxiety disorders are not exclusion criteria).
• Current use of tricyclic antidepressants or any antipsychotic medications, given the risk of seizure incidence independent of TMS use in tricyclics is up to 0.4% or second-generation antipsychotics up to 1.2%.
• Significant other medical disease such as unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, sleep apnea, or malignancy. Stable diabetes mellitus, stable hypertension (meaning that these conditions are followed up on by a physician and they are getting treatment for it with clinical stability), or hyperlipidemia are not exclusion criteria.
• History of traumatic brain injury
• History of epileptic disorders or family history of seizures in first degree relatives
• History of syncope
• History of tinnitus or hearing loss
• Current or history of substance misuse/dependence including alcohol at time of entry into the study.
• History of COVID-19 infection with persistent neurologic symptoms.
• Intra-axial implants (e.g., spinal cord stimulators or pumps) that are MRI incompatible.
• All exclusion criteria for MRI and TMS safety: any metallic implants, chips, or plates, cochlear implants, brain or skull abnormalities, aneurysm clips or coils, non-removable piercings, tattoos containing ferromagnetic ink, and claustrophobia.
• Surgery within the past 3 months or history of any brain surgery
• Pregnancy
• Participation into another research study
• In the judgment of the investigator, unable or unwilling to follow the protocol and instructions.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Other

Study locations

United States · 1 center

• University of Rochester Medical Center — Rochester

Identifiers

NCT: NCT07260864 · STUDY0000010795 · Schmitt program

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗