Repetitive Transcranial Magnetic Stimulation of Relief of Fibromyalgia Pain (TMSFFI)

August 31, 2024 updated by: Daniel Ciampi Araujo de Andrade, MD, PhD, University of Sao Paulo

Repetitive Transcranial Magnetic Stimulation of the Precentral-gyrus in the Relief of Fibromyalgia Pain: an International Multicenter Controlled Adaptative Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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. One of them refers to dosing of the treatment. rTMS sessions have been proposed to comprise from 1000 to 3000 pulses of stimulation in each session, which means that treatment sessions may last from 7 to 20 minutes. While there are positive studies reporting different numbers of pulses, the actual stimulation protocol chosen may impact not only the efficacy of the treatment, but also the duration of the stimulation session, the time patients stay at the health-care facility, and, thus, cost and compliance to treatment. 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 and patterned rTMS 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. Similarly, this technical approach allows for pre-planned interim analyses to be performed during data collection, allowing for the sample size to be readjusted during the trial, and, more importantly, allowing for trial termination due to futility or due to achievement of the primary endpoint before the end of the original preplanned data collection period, with lower risk of bias. Here, the adaptive approach will allow one not only to compare conventional rTMS (10Hz) to sham stimulation, but also, on second consecutive study, it will provide the first head-to-head study on rTMS to date comparing the analgesic effects of conventional (10Hz) and patterned (theta-burst) rTMS .

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Bernardo Do Campo, Brazil, 09606-070
        • Federal University of ABC
      • São Paulo, Brazil, 05403-010
        • Ambulatório de Fisioterapia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
    • Pernambuco
      • Recife, Pernambuco, Brazil, 50670-901
        • Universidade Federal de Pernambuco
    • SP
      • São Paulo, SP, Brazil, 05403900
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP)
  • France
      • Paris, France, 92100
        • Centre d'Evaluation et de Traitement de la Douleur Hôpital Ambroise Paré
  • Japan
      • Osaka, Japan, 565-0871
        • Department of Neuromodulation Osaka University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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).
  2. Age ≥18 years;
  3. Be able to understand study protocol and give signed, written informed consent
  4. Not under opioids
  5. VAS score ≥ 40/100 mm;

Exclusion Criteria:

  1. Known abuse of alcohol or illicit drugs
  2. Known psychiatric conditions
  3. 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);
  4. Not being under chronic contraceptive use (intrauterine dispositive or oral contraceptive)
  5. Other medical conditions demand hospitalization;
  6. Participation in other clinical studies at the same time

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Conventional rTMS - study 1
In study 1 patients were randomly allocated to receive conventional repetitive transcranial magnetic stimulation (10Hz).
Procedure: Conventional rTMS - study 1
Patients will be undergoing to 10Hz transcranial magnetic stimulation session
Experimental: Sham rTMS - study 1
In study 1 patients were randomly allocated to receive sham repetitive transcranial magnetic stimulation.
Procedure: Sham rTMS - study 1
Patients will be undergoing to sham transcranial magnetic stimulation session
Experimental: Conventional rTMS - study 2
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
Patients will be undergoing to 10Hz transcranial magnetic stimulation session
Experimental: Patterned rTMS - study 2
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
Patients will be undergoing to theta-burst transcranial magnetic stimulation session

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Analgesic effects of motor cortex stimulation
Time Frame: 8th week of treatment
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Global impression of change
Time Frame: 8th and 16th weeks of treatment
Assess % of very much and much improved
8th and 16th weeks of treatment
Pain intensity
Time Frame: At the end of the induction period (10th day) and 16th week
Measured by VAS (0 no pain -10 worst pain)
At the end of the induction period (10th day) and 16th week
Mood
Time Frame: 8th week of treatment
Assess mood by hospital anxiety and depression scale
8th week of treatment
Impact of fibromyalgia daily
Time Frame: 8th and 16th week of treatment
Assess by fibromyalgia impact questionnaire
8th and 16th week of treatment
Interference in daily activites
Time Frame: 8th week of treatment
Measured by brief pain inventory
8th week of treatment
Medication use
Time Frame: 8th week of treatment
Measured by Brief Pain Inventory
8th week of treatment
Phenotypical markers of analgesic response
Time Frame: 8th and 16th week of treatment
Assessment of phenotypical markers of analgesic response
8th and 16th week of treatment
Adverse events
Time Frame: 8th and 16th week of treatment
Assess of adverse events by standardized questionnaire'
8th and 16th week of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Sao Paulo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniel Ciampi de Andrade, MD, PhD, Pain Center, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 3, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 5, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 5, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 31, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RGDCA03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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