Chronic Pain, Fibromyalgia
Conditions
Keywords
Fibromyalgia, Transcranial Direct Current Stimulation, tDCS, Pregabalin, Functional Neuroimaging, Near Infrared Spectroscopy, NIRS, Chronic Pain, Transcranial Magnetic Stimulation, TMS
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.
Interventions
DRUGPregabalin
Pregabalin 150 mg per oral BID (i.e. twice per day).
OTHERTranscranial Direct Current Stimulation
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.
OTHERSham Transcranial Direct Current Stimulation
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.
Sponsors
Hospital de Clinicas de Porto Alegre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Level of depressive symptoms. | Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 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. Depression symptoms will be assessed using the Beck Depression Inventory, which covers neurovegetative symptoms of depression. It will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Three Evaluations. |
| Pain catastrophizing thoughts. | Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 after initiating the allocated intervention. | The level of catastrophic thinking will be assessed by the scale of catastrophic thoughts adapted to the Brazilian population (BP-PCS). Will be assessed before initiating treatment. Patients will receive pregabalin 150 mg PO BID + tDCS (or sham tDCS) daily during 2 weeks, and then twice per week until week 8th. Pain catastrophizing thoughts will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Three Evaluations. |
| Serum biomarkers levels: The brain derived neurotrophic factor, salivary cortisol, tumor necrosis factor alpha, Interleukin 1, 6 and 10 levels will be measured. | 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. |
| Sleep quality. | Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 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. Sleep quality will be assessed using the Pittsburgh Sleep Quality Index and the 10 cm scale of sleep quality. It will be assessed 2 and 8 weeks after initiating the allocated intervention. Total: Three Evaluations. |
Countries
Brazil
Contacts
Primary ContactWolnei Caumo, MD, PhD
Outcome results
None listed