Repetitive Transcranial Magnetic Stimulation of Relief of Fibromyalgia Pain

NCT03658694 | Completed DMC

• 1 other identifier: RGDCA03
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 6

Brief Summary

There are currently several points concerning rTMS for pain relief that have a huge impact in the practical application of rTMS in clinical practice, but which have not been approached by previous studies. Also, an even more important issue is the frequency of the sessions in each treatment protocol. The idea of performing stimulation in chronic pain patients on a consecutive daily basis for long-term treatments seem unrealistic and potentially costly. However, it has been reported in animals, healthy subjects and FM patients that the analgesic effects of rTMS can outlast the stimulation session for several minutes and even days. This has led to the proposal that pain treatment with rTMS could be performed in consecutive daily induction sessions, followed by spaced (weekly, fortnightly and even monthly) maintenance sessions. This approach is similar to what is performed routinely in patients with major depression treated by rTMS to the dorsolateral prefrontal cortex, and has successfully been tested in FM patients in a single- center study. Should this approach prove effective in larger prospective multicentric studies, rTMS could enter the armamentarium of non-invasive, non- pharmacological, low-adverse event therapeutic options to relieve fibromyalgia- related pain and associate symptoms. Hence, our aim is to conduct a multicentric international clinical trial on the influence of rTMS in the control of pain in a consecutive adaptive trial design where conventional rTMS (10Hz) and patterned rTMS (theta-burst) will be studied. Stimulations will be performed in a clinical practice-friendly approach, where daily maintenance sessions will be followed by weekly, and fortnightly stimulation sessions. There have been very scarce adaptive trials in the pain and non-invasive stimulation fields. This methodological approach allows for the use of lower number of patients in consecutive trials and, among other qualities, it allows for the imputation of data from the first trial into the second one, thus decreasing the duration of the studies and the number of participants.

Conditions

Fibromyalgia

Keywords

fibromyalgia; repetitive transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• Analgesic effects of motor cortex stimulation

  Percentage of responders based on the reduction of ≥50% in pain intensity (numerical rating scale 0-10) at the end of the study compared to baseline.

  8th week of treatment

Secondary Outcomes (8)

• Global impression of change

  8th and 16th weeks of treatment

• Pain intensity

  At the end of the induction period (10th day) and 16th week

• Mood

  8th week of treatment

• Impact of fibromyalgia daily

  8th and 16th week of treatment

• Interference in daily activites

  8th week of treatment

Study Arms (4)

Conventional rTMS - study 1

EXPERIMENTAL

In study 1 patients were randomly allocated to receive conventional repetitive transcranial magnetic stimulation (10Hz).

Procedure: Conventional rTMS - study 1

Sham rTMS - study 1

EXPERIMENTAL

In study 1 patients were randomly allocated to receive sham repetitive transcranial magnetic stimulation.

Procedure: Sham rTMS - study 1

Conventional rTMS - study 2

EXPERIMENTAL

In study 2, after the end of the first trial will be allocated to receive conventional of repetitive transcranial magnetic stimulation (10Hz).

Procedure: Conventional rTMS - study 2

Patterned rTMS - study 2

EXPERIMENTAL

In study 2, after the end of the first trial will be allocated to receive patterned of repetitive transcranial magnetic stimulation (Theta-burst).

Procedure: Patterned rTMS - stage 2

Interventions

Conventional rTMS - study 1 PROCEDURE

Patients will be undergoing to 10Hz transcranial magnetic stimulation session

Conventional rTMS - study 1

Sham rTMS - study 1 PROCEDURE

Patients will be undergoing to sham transcranial magnetic stimulation session

Sham rTMS - study 1

Conventional rTMS - study 2 PROCEDURE

Patients will be undergoing to 10Hz transcranial magnetic stimulation session

Conventional rTMS - study 2

Patterned rTMS - stage 2 PROCEDURE

Patients will be undergoing to theta-burst transcranial magnetic stimulation session

Patterned rTMS - study 2

Eligibility Criteria

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

You may qualify if:

• Female patients with diagnosis fibromyalgia according to the ACR 2016 criteria (patient satisfies modified 2016 fibromyalgia criteria if the following 3 conditions are met: 1) widespread pain index (WPI) ≥ 7 and symptom severity scale (SSS) score 5 OR WPI of 4-6 and SSS score ≥ 9. 2) Generalized pain, defined as pain in at least 4 of 5 regions, must be present. Jaw, chest, and abdominal pain are not included in generalized pain definition. 3) Symptoms have been generally present for at least 3 months. 4) A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses).
• Age ≥18 years;
• Be able to understand study protocol and give signed, written informed consent
• Not under opioids
• VAS score ≥ 40/100 mm;

You may not qualify if:

• Known abuse of alcohol or illicit drugs
• Known psychiatric conditions
• Contraindications to rTMS (42) (Head trauma or concussion, metal implants in the skull, pregnancy, cardiac pacemaker, medication infusion devices, previous troubles with TMS or MRI);
• Not being under chronic contraceptive use (intrauterine dispositive or oral contraceptive)
• Other medical conditions demand hospitalization;
• Participation in other clinical studies at the same time

Sponsors & Collaborators

• University of Sao Paulo: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (6)

Universidade Federal de Pernambuco

Recife, Pernambuco, 50670-901, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP)

São Paulo, São Paulo, 05403900, Brazil

Location

Federal University of ABC

São Bernardo do Campo, 09606-070, Brazil

Location

Ambulatório de Fisioterapia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, 05403-010, Brazil

Location

Centre d'Evaluation et de Traitement de la Douleur Hôpital Ambroise Paré

Paris, 92100, France

Location

Department of Neuromodulation Osaka University

Osaka, 565-0871, Japan

Location

Related Publications (1)

• Lins CC, Fonseca AS, Martins PN, Oliveira JCB, Fernandes AM, Baptista AF, Kubota GT, da Silva VA, Teixeira MJ, de Andrade DC. Investigation of predictors of pain relief with high-frequency repetitive motor cortex transcranial magnetic stimulation among people with fibromyalgia. Neurophysiol Clin. 2025 Nov;55(6):103109. doi: 10.1016/j.neucli.2025.103109. Epub 2025 Oct 4.

  PMID: 41046849 DERIVED

MeSH Terms

Conditions

Fibromyalgia

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Daniel Ciampi de Andrade, MD, PhD

  Pain Center, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pain Center of Department of Neurology

Model Details: This is an adaptive sequential trial of FM patients. In stage 1 patients were randomly allocated into two parallel arms (conventional rTMS, sham) using adaptive methodology. In stage 2, after the end of the first trial, patients will be allocated to two arms (conventional rTMS, patterned rTMS). Both stages will be conducted in a sequential methodology where an interim analysis will take place and indicate whether will take place trial is positive and of the scientific board agrees open its start. Recruitment time will be extended by 12 months due to dropouts related to the Covid-19 pandemic. We have had dropouts due to some patients who developed Covid-19 and also due to patients who were afraid of becoming infected during hospital visits. Those patients who dropped out of the study due to the pandemic will be excluded from the main analysis and will be analyzed as a secondary outcome.

Study Record Dates

• First Submitted: September 3, 2018
• First Posted: September 5, 2018
• Study Start: April 1, 2019
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: September 5, 2024

Record last verified: 2023-10

Locations

JP (1); BR (4); FR (1)