Effect of tDCS in Intrinsic Functional Brain Connectivity Assessed by Functional Magnetic Resonance in Fibromyalgia

Effect of Transcranial Continuous Current Neuromodulation in Intrinsic Functional Brain Connectivity Assessed by Functional Magnetic Resonance Imaging (fMRI) in Fibromyalgia: A Randomized, Double-blind Controlled Trial

Considering the central component of fibromyalgia (FM), the focus of research on current therapeutic approaches has been techniques that may modify the dysfunctional neuroplasticity process, such as transcranial direct current (tDCS) stimulation in order to counteract the dysfunction responsible for triggering and maintain the symptoms of FM. Although this technique is gaining space in research and in the clinical scenario, many questions remain to be answered, such as time of treatment, place to be stimulated and neurophysiological clarification of the mechanisms involved.

Based on the presented scenario, the present project was organized, being a double-blinded parallel randomized controlled trial with 20 female patients with FM diagnosed according to the criteria of the American Society of Rheumatology (2010 - reviewed in 2016) between 19 and 65 years of age, randomized to receive active or simulated anodic pole over the left dorsolateral prefrontal cortex (DLPFC) (10 patients in each group). Twenty 20-minute sessions, with a current intensity of 2 milliamperes, will be performed.

In order to respond to the objectives of this study, the IFC will be evaluated before and after the intervention, through rs-fMRI using seed-based correlation analysis (SCA). The investigators have a secondary objective to correlate structural connectivity through the technique of diffusion tensors imaging (DTI) with measures of pain, functional capacity, depressive symptoms and catastrophism to pain.

The hypothesis is that in FM there is a syndrome of dysfunction in basal intrinsic functional connectivity (IFC) and that the tDCS has a neuromodulatory effect capable of reducing connectivity between brain areas related to chronic pain and other neuropsychiatric components of FM, such as the ventrolateral thalamus, cortex motor, prefrontal cortex, insular cortex, hippocampus, periaqueductal gray matter, among others. The investigators believe that a higher cortico-thalamic IFC and between regions with high density of opioid receptors have a positive predictive response in the treatment of tDCS.

Study Overview

• Status: Unknown
• Conditions: Fibromyalgia
• Intervention / Treatment: Device: Active-tDCS; Device: Sham-tDCS

Detailed Description

Fibromyalgia (FM) is a syndrome that is characterized by generalized musculoskeletal pain, fatigue, unrepairable sleep, cognitive alterations, depressive and neurovegetative symptoms, whose neurobiological process is multiple and complex. Although it is of great relevance to the individual and to society, this pathology often does not receive the necessary attention by the organs that define the priorities of health care. Population prevalence, according to the criteria of the American Society of Rheumatology, reaches 5.4%, and the costs of care, taxes and early retirement due to disability are estimated at more than the US $ 29 billion per year in the United States. It is known that conventional pharmacological therapies produce insignificant responses in more than 50% of patients. It is postulated that these high rates of failure are due in part to a lack of knowledge about pathophysiological mechanisms. What is known so far is that the peripheral mechanisms contribute to the FM picture, but dysfunction in central neurobiological pathways surely commands the process, perpetuating the dysfunctional process that includes central sensitization (CS). CS comprises the symptoms of fibromyalgia syndrome that culminates in a state of hypersensitivity that expresses the imbalance of the excitation/inhibition processes that sustain this condition of non-pathological pain. Functional alterations of the motor cortex and its connections with subcortical structures that constitute the neuromatrix of pain have now been demonstrated. Functional magnetic resonance imaging (fMRI), using the resting-state fMRI (rs-fMRI) technique, has also demonstrated that high intrinsic functional connectivity (IFC) is related to pain intensity on FM.

Considering the central component of FM, the focus of research on current therapeutic approaches has been techniques that may modify the dysfunctional neuroplasticity process, such as transcranial direct current (tDCS) stimulation in order to counteract the dysfunction responsible for triggering and maintain the symptoms of FM. Although this technique is gaining space in research and in the clinical scenario, many questions remain to be answered, such as time of treatment, place to be stimulated and neurophysiological clarification of the mechanisms involved.

Based on the presented scenario, the present project was organized, being a double-blinded parallel randomized controlled trial with 20 female patients with FM diagnosed according to the criteria of the American Society of Rheumatology (2010 - reviewed in 2016) between 19 and 65 years of age, randomized to receive active or simulated anodic pole over the left dorsolateral prefrontal cortex (DLPFC) (10 patients in each group). Twenty 20 minute sessions, with a current intensity of 2 milliampere, will be performed.

In order to respond to the objectives of this study, the IFC will be evaluated before and after the intervention, through rs-fMRI using seed-based correlation analysis (SCA). The investigators have a secondary objective to correlate structural connectivity through the technique of diffusion tensors imaging (DTI) with measures of pain, functional capacity, depressive symptoms and catastrophism to pain.

The hypothesis is that in FM there is a syndrome of dysfunction in basal IFC and that the tDCS has a neuromodulatory effect capable of reducing connectivity between brain areas related to chronic pain and other neuropsychiatric components of FM, such as the ventrolateral thalamus, cortex motor, prefrontal cortex, insular cortex, hippocampus, periaqueductal gray matter, among others. The investigators believe that a higher cortico-thalamic IFC and between regions with high density of opioid receptors have a positive predictive response in the treatment of tDCS.

If the hypothesis is proven, the IFC data may serve as a biological marker associated with the perception of pain and its clinical presentation, and consequently, open the possibility of including IFC as a diagnostic parameter and therapeutic response. In addition to the possible contribution to knowledge production, this project aims to transfer the technology acquired and developed to the community, and thus benefit millions of people suffering from chronic FM pain with limited diagnostic and therapeutic perspectives, as well as extending the knowledge acquired for other neuropsychiatric disorders, such as depression.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90.450-120
      • Recruiting
      • Hospital de Clinicas de Porto Alegre
      • Sub-Investigator: Matheus D Soldatelli, MD
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
      • Recruiting
      • Hospital de Clinicas e Porto Alegre (HCPA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Literate
• Female, between 18 and 65 years old
• With the diagnosis of fibromyalgia according to the criteria of the American College of Rheumatology (2010-2016)
• Pain score equal to or greater than six on the Numerical Pain Scale (NPS 0-10) on most days of the last 3 months.
• Give informed consent to participate after the initial evaluation.

Exclusion Criteria:

• Living outside the city of Porto Alegre, RS, Brazil
• Pregnancy
• Severe Mental Illness
• tDCS contraindications
• Magnetic resonance imaging (MRI) contraindications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active-tDCS; 10 patients will receive Active-tDCS intervention (2mA, 20 min) at home.	Device: Active-tDCS; Active home-based tDCS applied at home. 5 days a week for 4 weeks.
Sham Comparator: Sham-tDCS; 10 patients will receive Sham-tDCS intervention (2mA, 20 min) at home.	Device: Sham-tDCS; Sham home-based tDCS applied at home. 5 days a week for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Functional cerebral connectivity(rs-fMRI)to post-intervention rs-fMRI	Evaluation of functional cerebral connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) between the change in baseline and post-intervention assessments.	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural cerebral connectivity	Evaluation of structural cerebral connectivity using diffusion tract imaging (DTI)	30 minutes

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: August 4, 2018
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 12, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: tDCS; fibromyalgia; fMRI; rs-fMRI
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: 2018-0353

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No