Functional Neuroimaging in Fibromyalgia Patients Receiving tDCS

Study of the Brain With Optic Functional Neuroimaging in Patients With Chronic Pain Using Transcranial Direct Current Stimulation

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Pain; Fibromyalgia
• Intervention / Treatment: Drug: Pregabalin; Other: Sham Transcranial Direct Current Stimulation; Other: 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 Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Recruiting
      • Hospital de Clínicas de Porto Alegre
      • Contact: Wolnei Caumo, MD, PhD; Phone Number: (51) 3359 8083; Email: caumo@cpovo.net
      • Principal Investigator: Wolnei Caumo, MD PhD

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:

• - 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Pregabalin, Sham tDCS; 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.	Drug: Pregabalin; Pregabalin 150 mg per oral BID (i.e. twice per day).; Other Names: Lyrica; Other: Sham 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.; Other Names: Sham tDCS
Experimental: Pregabalin, tDCS; 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.	Drug: Pregabalin; Pregabalin 150 mg per oral BID (i.e. twice per day).; Other Names: Lyrica; Other: Transcranial 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.; Other Names: tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the pressure pain threshold.	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.	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.
Change in cortical excitability parameters assessed by transcranial magnetic stimulation.	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.	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.
Changes in motor cortex blood flow assessed by near infrared spectroscopy.	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the temperature pain threshold.	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.	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.
Change in the visual analogue scale for pain to prolonged thermal stimuli.	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.	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.
Change in average daily pain assessed with the visual analogue scale.	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.	Starting on day 1, each day until Week 12. Total: 84 Evaluations.
Change in the Fibromyalgia Impact Questionnaire.	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.	Day 1 (1 hour before receiving the 1st dose of pregabalin); week 2, week 8 and week 12 after initiating the allocated intervention.
Change in quality of life assessed by the WHOQOL (World Health Organization Quality of Life), reduced form, adapted to Brazilian Portuguese.	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.	Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2, week 8 and week 12 after initiating the allocated intervention.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum biomarkers levels: The brain derived neurotrophic factor, salivary cortisol, tumor necrosis factor alpha, Interleukin 1, 6 and 10 levels will be measured.	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.	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.
Level of depressive symptoms.	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.	Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 after initiating the allocated intervention.
Sleep quality.	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.	Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 after initiating the allocated intervention.
Pain catastrophizing thoughts.	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.	Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 after initiating the allocated intervention.

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Wolnei Caumo, MD, PhD, Hospital de Clínicas de Porto Alegre

Publications and helpful links

General Publications

• Nitsche MA, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, Henning S, Tergau F, Paulus W. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003 Nov 15;553(Pt 1):293-301. doi: 10.1113/jphysiol.2003.049916. Epub 2003 Aug 29.
• Ziemann U, Lonnecker S, Steinhoff BJ, Paulus W. Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study. Ann Neurol. 1996 Sep;40(3):367-78. doi: 10.1002/ana.410400306.
• Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum. 2006 Dec;54(12):3988-98. doi: 10.1002/art.22195.
• Burgmer M, Pogatzki-Zahn E, Gaubitz M, Wessoleck E, Heuft G, Pfleiderer B. Altered brain activity during pain processing in fibromyalgia. Neuroimage. 2009 Jan 15;44(2):502-8. doi: 10.1016/j.neuroimage.2008.09.008. Epub 2008 Sep 24.
• Arnold LM. Biology and therapy of fibromyalgia. New therapies in fibromyalgia. Arthritis Res Ther. 2006;8(4):212. doi: 10.1186/ar1971.
• Russell IJ, Raphael KG. Fibromyalgia syndrome: presentation, diagnosis, differential diagnosis, and vulnerability. CNS Spectr. 2008 Mar;13(3 Suppl 5):6-11. doi: 10.1017/s1092852900026778.
• Chizh BA, Gohring M, Troster A, Quartey GK, Schmelz M, Koppert W. Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers. Br J Anaesth. 2007 Feb;98(2):246-54. doi: 10.1093/bja/ael344.
• Dooley DJ, Mieske CA, Borosky SA. Inhibition of K(+)-evoked glutamate release from rat neocortical and hippocampal slices by gabapentin. Neurosci Lett. 2000 Feb 18;280(2):107-10. doi: 10.1016/s0304-3940(00)00769-2.
• Taber KH, Hillman EM, Hurley RA. Optical imaging: a new window to the adult brain. J Neuropsychiatry Clin Neurosci. 2010 Fall;22(4):iv, 357-60. doi: 10.1176/jnp.2010.22.4.iv. No abstract available.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Anticipated): July 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 22, 2013

Study Record Updates

• Last Update Posted (Estimate): July 22, 2013
• Last Update Submitted That Met QC Criteria: July 17, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: tDCS; Chronic Pain; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation; Functional Neuroimaging; Fibromyalgia; Pregabalin; TMS; Near Infrared Spectroscopy; NIRS
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Chronic Pain; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: 120128