Functional Neuroimaging in Fibromyalgia Patients Receiving tDCS

Phase 2

• Conditions: Fibromyalgia; Chronic Pain
• Interventions: Drug: Pregabalin; Other: Sham Transcranial Direct Current Stimulation; Other: Transcranial Direct Current Stimulation

• Registration Number: NCT01904097
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

Brief Summary

The purpose of this study is to evaluate effectiveness and cerebral neuronal ability to adaptation in patients with fibromyalgia who receive pregabalin and transcranial direct current stimulation.

Detailed Description

Fibromyalgia syndrome occurs in around 2% of the population (predominantly women), and is characterized by its poor response to conventional therapies. Therapeutic approaches modulating inhibitory pathways, including pharmacologic options as pregabalin, and non pharmacological ones as transcranial direct current stimulation (tDCS) have been proven to be of limited utility independently. Aiming to evaluate a better understanding of the pathophysiogenic mechanisms and the effect of these treatments on neuroplasticity, this study was designed evaluating neurophysiologic, neurochemical and clinical parameters. Neurophysiologic parameters and functions to be assessed will include pain threshold, motor evoked potential, silent period, intracortical facilitation and inhibition assessed by Transcranial Magnetic Stimulation (TMS) and optic functional neuroimaging. Neurochemical measurements considered will be neurotrophins (BDNF) and inflammatory mediators (TNF, IL1, IL6, IL10 and cortisol). Clinical characteristics will be assessed using validated scales capable to detect functional capacity, quality of life (WHOCOHL), catastrophism, sleep disruptions (Pittsburgh) and depressive symptoms (Beck Depression Inventory). Considering the above described hypothesis, the present randomized clinical trial with blinded patients and evaluators is proposed. It pretends to analyze short-, mid- and long-term neurobiological mechanisms triggered by the selected interventions.

Study Timeline

• Study Start: 2013-03
• Status Verified: 2013-07
• Study First Submitted: 2013-07-08
• Study First Submitted QC: 2013-07-17
• Last Update Submitted: 2013-07-17
• Study First Posted: 2013-07-22
• Last Update Posted: 2013-07-22
• Primary Completion: 2014-07
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 34

Inclusion Criteria

• • Diagnosis of fibromyalgia according to the American College of Rheumatology criteria

Exclusion Criteria

• Psychiatric or neurologic disorder that unable patient to consent and follow study protocol.
• De-compensated systemic disease.
• Chronic inflammatory disease (e.g. Systemic Lupus Erythematous, Rheumatoid Arthritis).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pregabalin, Sham tDCS	Sham Transcranial Direct Current Stimulation	Patients will receive pregabalin 150 mg oral (PO) twice per day (BID), and sham transcranial direct current stimulation (sham tDCS) five times per week during 2 weeks, and then twice per week until week 8th. The sham tDCS consists of the same montage of the active tDCS, but the device is turned off 30 seconds after initiating stimulation (without letting the patient notice it). Rest of the montage is kept identical as the active one during the 30 minutes that the session lasts.
Pregabalin, tDCS	Transcranial Direct Current Stimulation	Patients will receive pregabalin 150 mg oral(PO) twice per day (BID), and transcranial direct current stimulation (tDCS) five times per week during 2 weeks, and then twice per week until week 8th. The tDCS consists of application of low intensity direct current (2 mA), with the anode placed in the dominant motor cortex (M1) and the cathode in the ipsilateral supraorbital region during 30 minutes each session, using sponge electrodes soaked with normal saline solution.
Pregabalin, Sham tDCS	Pregabalin	Patients will receive pregabalin 150 mg oral (PO) twice per day (BID), and sham transcranial direct current stimulation (sham tDCS) five times per week during 2 weeks, and then twice per week until week 8th. The sham tDCS consists of the same montage of the active tDCS, but the device is turned off 30 seconds after initiating stimulation (without letting the patient notice it). Rest of the montage is kept identical as the active one during the 30 minutes that the session lasts.
Pregabalin, tDCS	Pregabalin	Patients will receive pregabalin 150 mg oral(PO) twice per day (BID), and transcranial direct current stimulation (tDCS) five times per week during 2 weeks, and then twice per week until week 8th. The tDCS consists of application of low intensity direct current (2 mA), with the anode placed in the dominant motor cortex (M1) and the cathode in the ipsilateral supraorbital region during 30 minutes each session, using sponge electrodes soaked with normal saline solution.

Primary Outcome Measures

Name	Time	Method
Changes in motor cortex blood flow assessed by near infrared spectroscopy.	Day 1 (1 hour before receiving the 1st dose of pregabalin; and 1 hour after the first dose of pregabalin); week 2 and week 8 after initiating the allocated intervention.	Will be assessed before and 1 hour after a single dose of 150 mg of Pregabalin. Patients will also receive pregabalin 150 mg BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Motor cortex blood flow will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Four Evaluations.
Change in the pressure pain threshold.	Day 1 (1 hour before receiving the 1st dose of pregabalin; and 1 hour after the first dose of pregabalin); week 2 and week 8 after initiating the allocated intervention.	Assessed with pressure algometer. Will be assessed before and 1 hour after a single dose of 150 mg of Pregabalin. Patients will also receive pregabalin 150 mg BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Pain thresholds will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Four evaluations.
Change in cortical excitability parameters assessed by transcranial magnetic stimulation.	Day 1 (1 hour before receiving the 1st dose of pregabalin; and 1 hour after the first dose of pregabalin); week 2 and week 8 after initiating the allocated intervention.	Will be assessed before and 1 hour after a single dose of 150 mg of Pregabalin. Patients will also receive pregabalin 150 mg BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Cortical Excitability will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Four Evaluations.

Secondary Outcome Measures

Name	Time	Method
Change in the temperature pain threshold.	Day 1 (1 hour before receiving the 1st dose of pregabalin; and 1 hour after the first dose of pregabalin); week 2 and week 8 after initiating the allocated intervention.	Will be assessed before and 1 hour after a single dose of 150 mg of Pregabalin. Patients will also receive pregabalin 150 mg BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Pain thresholds will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Four Evaluations.
Change in the visual analogue scale for pain to prolonged thermal stimuli.	Day 1 (1 hour before receiving the 1st dose of pregabalin; and 1 hour after the first dose of pregabalin); week 2 and week 8 after initiating the allocated intervention.	Will be assessed before and 1 hour after a single dose of 150 mg of Pregabalin. Patients will also receive pregabalin 150 mg BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Pain to prolonged thermal stimuli will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Four Evaluations.
Change in average daily pain assessed with the visual analogue scale.	Starting on day 1, each day until Week 12. Total: 84 Evaluations.	Patients will be asked to daily write down their average pain level (assessed by the Visual Analogue Scale, self-administered) in a paper diary. Total evaluations: 84.
Change in the Fibromyalgia Impact Questionnaire.	Day 1 (1 hour before receiving the 1st dose of pregabalin); week 2, week 8 and week 12 after initiating the allocated intervention.	Will be assessed before initiating treatment. Patients will receive pregabalin 150 mg BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Fibromyalgia Impact Questionnaire will be assessed 2, 8 and 12 weeks after initiating the allocated intervention. Total: Four Evaluations.
Change in quality of life assessed by the WHOQOL (World Health Organization Quality of Life), reduced form, adapted to Brazilian Portuguese.	Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2, week 8 and week 12 after initiating the allocated intervention.	Will be assessed before initiating treatment. Patients will receive pregabalin 150 mg BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Quality of life will be assessed 2, 8 and 12 weeks after initiating the allocated intervention. Total: Four Evaluations.

Trial Locations

Locations (1)

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande do Sul, Brazil