Repetitive Transcranial Magnetic Stimulation of Relief of Fibromyalgia Pain

Fibromyalgia Clinical Trial

— TMSFFI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03658694
• Other study ID #: RGDCA03
• Status: Completed
• Phase: N/A
• Start date: April 1, 2019
• Est. completion date: March 1, 2023

Study information

• Verified date: October 2023
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 1, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

Intervention

Procedure:
• Conventional rTMS - study 1
Patients will be undergoing to 10Hz transcranial magnetic stimulation session
• Sham rTMS - study 1
Patients will be undergoing to sham transcranial magnetic stimulation session
• Conventional rTMS - study 2
Patients will be undergoing to 10Hz transcranial magnetic stimulation session
• Patterned rTMS - stage 2
Patients will be undergoing to theta-burst transcranial magnetic stimulation session

Locations

Country	Name	City	State
Brazil	Universidade Federal de Pernambuco	Recife	Pernambuco
Brazil	Federal University of ABC	São Bernardo Do Campo
Brazil	Ambulatório de Fisioterapia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP)	São Paulo	SP
France	Centre d'Evaluation et de Traitement de la Douleur Hôpital Ambroise Paré	Paris
Japan	Department of Neuromodulation Osaka University	Osaka

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Countries where clinical trial is conducted

Brazil,  France,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Global impression of change	Assess % of very much and much improved	8th week of treatment
Secondary	Pain intensity	Measured by VAS (0 no pain -10 worst pain)	At the end of the induction period (10th day) and 12th week
Secondary	Mood	Assess mood by hospital anxiety and depression scale	baseline and 12th week
Secondary	Medication use	Measured by Brief Pain Inventory	baseline and 12th week
Secondary	Interference in daily activites	Measured by brief pain inventory	baseline and 12th week
Secondary	Impact of fibromyalgia daily	Assess by fibromyalgia impact questionnaire	baseline and 12th week
Secondary	Phenotypical markers of analgesic response	Assessment of phenotypical markers of analgesic response	baseline and 12th week
Secondary	Adverse events	Assess of adverse events by standardized questionnaire'	baseline and 12th week