Clinical trial NCT05963321: Cortical Excitability Modulation With ctDCS in Fibromyalgia.
Official title: Cortical Excitability Modulation With Cerebellar Transcranial Direct Current Stimulation in Fibromyalgia: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fibromyalgia
Chronic Pain
Keywords: Fibromyalgia
Cerebellum
Transcranial direct current magnetic stimulation
Transcranial magnetic stimulation
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 92
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Fibromyalgia is a syndrome characterized by chronic generalized musculoskeletal pain, accompanied by other symptoms such as fatigue, sleep disturbance and depression. Complaints of memory deficit, cognitive dysfunction, headache and gastrointestinal disorders are also common. Although it is a relatively common syndrome, exist a limited effectiveness of the pharmacologycal treatment. However, In the last years new therapeutic and diagnostic options have been sought. This scenario includes the use of different techniques of non-invasive brain stimulation, such as transcranial direct current magnetic stimulation (tDCS) and transcranial magnetic stimulation (TMS), which have already had promising results in reducing pain. Based on the above, the objective of this research is to evaluate the effect of cerebellar tDCS on clinical measures of pain and cortical excitability in patients with fibromyalgia. In this study, the intervention consists of a single tDCS session in which two devices will be used simultaneously. The active electrode will be placed in the cerebellum and/or in the primary motor cortex and the cathode in the contralateral supraorbital region. It is expected that the application of this protocol will be able to have a modulatory effect on clinical pain measures. In addition to producing changes in cortical excitability as a reflection of the integration between the cerebellum-thalamus-cortical pathways.

Detailed description: The prevalence of fibromyalgia is approximately 2.7%, with a female-to-male ratio of 3:1. Although it is a relatively common syndrome, there are many doubts regarding its diagnosis and pathophysiology. In addition to the previously mentioned questions, this pathology has high social costs due to its association with the loss of labor productivity and it is characterized by being unresponsive to pharmacological treatment. Given the limited effectiveness of available therapeutic options, new therapeutic and diagnostic options have been sought. This scenario includes the use of different techniques of non-invasive brain stimulation, such as transcranial direct current magnetic stimulation (tDCS) and transcranial magnetic stimulation (TMS), which have already had promising results in reducing pain. In addition, TMS also allows measuring parameters that help to understand the reorganization of physiological processes. In this study, TMS is used to understand the pathophysiology of fibromyalgia, while tDCS allows modulating the excitability of the neuronal membrane potential of cortical and subcortical neural networks, producing a neuromodulatory effect of the top-down type. According to the evidence, the greatest impact on pain is associated with stimulation of the primary motor cortex (M1), but recent studies have shown the possible relationship between stimulation of extracerebral regions such as the cerebellum, with an analgesic effect present in healthy individuals and patients with different pathologies. In the same way, the cortical excitability measures obtained through TMS allow us to identify the imbalance between inhibitory and excitatory systems, related to pain perception and the analgesic response of endogenous mechanisms. In this research, our objective is to evaluate the effect of cerebellar tDCS on clinical measures of pain and cortical excitability in patients with fibromyalgia. This is a randomized, double-blind, controlled clinical trial, parallel, which has as its primary outcome, the evaluation of the variations in motor evoked potential (MEP) (neurophysiological outcome) and the numerical pain scale (NPS) 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 modulatory 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 a single tDCS session in which two devices will be used simultaneously. The active electrode will be placed 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 supraorbital 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 and composed of 23 individuals each.

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 4 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.

Primary outcomes:
measure: Change in motor evoked potential (MEP).
timeFrame: Up to 60 minutes after tDCS onset.
measure: Change in pain level
timeFrame: Up to 60 minutes after tDCS onset.
Secondary outcomes:
measure: Change in the Brief Pain Inventory (BPI) score
timeFrame: Up to 15 days after tDCS onset.
measure: Change in Function of corticospinal pathway
timeFrame: Up to 60 minutes after tDCS onset.
measure: change in conditioned pain modulation (CPM)
timeFrame: Up to 60 minutes after tDCS onset.
measure: Change in the quantitative sensory test (QST)
timeFrame: Up to 60 minutes after tDCS onset.
Other outcomes:
measure: levels of Brain derived neurotrophic factor
timeFrame: Blood samples will be collected at baseline, before tDCS onset.
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital de clinicas de Porto Alegre
state: Rio Grande Do Sul
Study officials:
affiliation: Hospital de Clinicas de Porto Alegre
name: Wolnei Caumo, PhD
role: STUDY_DIRECTOR
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