Cortical Excitability Modulation With ctDCS in Fibromyalgia.

Study Overview
=================
Brief Summary
-----------------
In this research, the objective is to evaluate the effect of cerebellar tDCS on clinical measures of pain and cortical excitability in participants with fibromyalgia. This is a randomized, double-blind, controlled clinical trial that has as its primary outcome the evaluation of the variations in motor evoked potential (MEP) (a neuropsychological outcome) and the visual analog scale (VAS) as a clinical outcome.

Detailed Description
-----------------
In this research, the objective is to evaluate the effect of cerebellar tDCS on clinical measures of pain and cortical excitability in participants with fibromyalgia. This is a randomized, double-blind, controlled clinical trial that has as its primary outcome the evaluation of the variations in motor evoked potential (MEP) (a neuropsychological outcome) and the visual analog scale (VAS) as a clinical outcome. Secondary outcomes include the silent period (CSP), intra-cortical facilitation (ICF), and intra-cortical inhibition (ICI) obtained through TMS, the function of the descending modulator path of pain by the conditioned modulation test (CPM test), the Brief Pain Inventory (BPI), and the pain thresholds by heat, pressure, and cold. The intervention consists of an tDCS session in which the active electrode will be located in the cerebellum and/or in the primary motor cortex (4 stimulation protocols that will be implemented: active cerebellum electrode- active M1 electrode, sham cerebellum electrode - active M1 electrode, active cerebellum-M1 sham electrode, sham cerebellum electrode-M1 sham electrode) and the cathode in the contralateral supra orbital region. The equipment will apply a current of 2 mA for 20 minutes. In total, there will be 92 patients, divided into 4 intervention blocks composed of 23 individuals each.

Official Title
-----------------
Cortical Excitability Modulation With Cerebellar Transcranial Direct Current Stimulation in Fibromyalgia: a Randomized Clinical Trial

Conditions
-----------------
Fibromyalgia, Chronic Pain

Intervention / Treatment
-----------------
* Device: TDCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Right-handed women aged 18 to 65 years; who can read and write Confirmed diagnosis of fibromyalgia according to the criteria of the American College of Rheumatology (2010-2016). Pain score equal to or greater than 6 on the Numerical Pain Scale (Score 0-10) on most days in the last 3 months. Exclusion Criteria: Reside outside Porto Alegre area. Confirmed pregnancy Contraindications to TMS and tDCS: metallic implant in the brain; medical devices implanted in the brain, heart pacemaker; cochlear implant; history of alcohol or drug abuse in the last 6 months; neurological pathologies; hx of head trauma or neurosurgery; decompensated systemic diseases and chronic inflammatory diseases (lupus, rheumatoid arthritis, Reiter's syndrome); uncompensated hypothyroidism; personal history of cancer, past or undergoing treatment. Participants with diagnosis or recent contact with COVID will be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active cerebellum electrode and active M1 electrode<br>Two tDCS devices will be used simultaneously. In cerebellar stimulation (active), the anodal electrode will be positioned on the right side, with the center of the sponge approximately 3 cm from the ion; on the other hand, in cortical stimulation (active), the anodal electrode will be located in the left primary motor cortex. In both cerebellar and cortical stimulations, the cathode will be positioned in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes. | Device: TDCS<br>* Two tDCS devices will be used simultaneously. The intervention consists of a tDCS session in which the active electrode will be located in the cerebellum and/or in the primary motor cortex (4 stimulation protocols that will be implemented; active cerebellum electrode and active M1 electrode, sham cerebellum electrode and active M1 electrode, active cerebellum and sham M1 electrode, sham cerebellar electrode and sham M1 electrode) and the cathode in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes.<br>|
| Active Comparator: Sham cerebellar electrode and active M1 electrode<br>Two tDCS devices will be used simultaneously. In cerebellar stimulation (sham), the anodal electrode will be positioned on the right side, with the center of the sponge approximately 3 cm from the ion; on the other hand, in cortical stimulation (active), the anodal electrode will be located in the left primary motor cortex. In both cerebellar and cortical stimulations, the cathode will be positioned in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes. | Device: TDCS<br>* Two tDCS devices will be used simultaneously. The intervention consists of a tDCS session in which the active electrode will be located in the cerebellum and/or in the primary motor cortex (4 stimulation protocols that will be implemented; active cerebellum electrode and active M1 electrode, sham cerebellum electrode and active M1 electrode, active cerebellum and sham M1 electrode, sham cerebellar electrode and sham M1 electrode) and the cathode in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes.<br>|
| Active Comparator: Active cerebellum electrode and sham M1 electrode<br>Two tDCS devices will be used simultaneously. In cerebellar stimulation (active), the anodal electrode will be positioned on the right side, with the center of the sponge approximately 3 cm from the ion; on the other hand, in cortical stimulation (sham), the anodal electrode will be located in the left primary motor cortex. In both cerebellar and cortical stimulations, the cathode will be positioned in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes | Device: TDCS<br>* Two tDCS devices will be used simultaneously. The intervention consists of a tDCS session in which the active electrode will be located in the cerebellum and/or in the primary motor cortex (4 stimulation protocols that will be implemented; active cerebellum electrode and active M1 electrode, sham cerebellum electrode and active M1 electrode, active cerebellum and sham M1 electrode, sham cerebellar electrode and sham M1 electrode) and the cathode in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes.<br>|
| Sham Comparator: Sham cerebellar electrode and sham M1 electrode<br>Two tDCS devices will be used simultaneously. In cerebellar stimulation (sham), the anodal electrode will be positioned on the right side, with the center of the sponge approximately 3 cm from the ion; on the other hand, in cortical stimulation (sham), the anodal electrode will be located in the left primary motor cortex. In both cerebellar and cortical stimulations, the cathode will be positioned in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes | Device: TDCS<br>* Two tDCS devices will be used simultaneously. The intervention consists of a tDCS session in which the active electrode will be located in the cerebellum and/or in the primary motor cortex (4 stimulation protocols that will be implemented; active cerebellum electrode and active M1 electrode, sham cerebellum electrode and active M1 electrode, active cerebellum and sham M1 electrode, sham cerebellar electrode and sham M1 electrode) and the cathode in the contralateral supraorbital region. The equipment will apply a current of 2 mA for 20 minutes.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in motor evoked potential (MEP). | Change from before and after tDCS onset on MEP. Assessed by a variation in the amplitude obtained by 20 stimuli with an intensity of 120% of the MT. The MEP will be considered the arithmetic mean of the amplitude of the wave recorded by the EMG. | Up to 60 min after tDCS onset. | 
| Change in pain level | Change from before and after tDCS onset on Pain scores assessed by a visual analogue scale (VAS 0 to 100mm) (0 means no pain - 100 means the worst pain imaginable) | Up to 60 min after tDCS onset. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Brief Pain Inventory (BPI) score | It is a quick, simple, and easy-to-apply questionnaire that allows a multidimensional pain assessment to be carried out. The BPI consists of 15 items that determine the severity, existence, location, functional interference, applied therapeutic strategies, and efficacy of pain treatment. In the research, this questionnaire will be implemented at baseline, 8 and 15 days after tDCS onset. | Up to 15 days after tDCS onset. | 
| Change in other measures obtained through transcranial magnetic stimulation | Other measures of cortical excitability obtained through TMS include the silent period (CSP), intra-cortical facilitation (ICF) and intra-cortical inhibition (SICI). The TMS measures will be performed at two different times: before and after tDCS onset. | Up to 60 min after tDCS onset. | 
| change in conditioned pain modulation (CPM) | Conditioned pain modulation (CPM) is an experimental psychophysical measure that assesses supraspinal descending inhibitory mechanisms of pain modulation. In practice, a constant noxious stimulus (conditioning stimulus) is applied to one part of the body and a phasic stimulus (stimulus to be tested) to a distant part of the body before, during, and after the conditioning stimulus. The CPM is analyzed through the reduction that occurs in the perception of pain in the test stimulus.The conditioned pain modulation will be performed at two different times: before and after the single tDCS onset. | Up to 60 min after tDCS onset. | 
| Change in the quantitative sensory test (QST) | The quantitative sensory test (QST) evaluates the function of myelinated, small and unmyelinated fibers, also including the function of the spinothalamic tract and nociceptive fibers. In addition, the QST represents a non-invasive method, which determines the gain or loss of sensory perception in response to external stimuli of controlled intensity in a previously determined body area. The following tests will be carried out in the research: Painful pressure threshold: performed with a pressure algometer, applied on the upper extremity. Cold pressor test: the patient puts his extremity in a container with ice. The tolerance time will be determined. Sensation of heat: using a heat electrode applied to the extremity corresponding to the sensitive alteration, the first sensation of heat and the painful threshold of light, medium and maximum heat will be evaluated. The QST measures will be performed at two different times; before and after the tDCS onset. | Up to 60 min after tDCS onset. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fibromyalgia, Cerebellum, Transcranial direct current magnetic stimulation, Transcranial magnetic stimulation