Clinical trial NCT01904097: Functional Neuroimaging in Fibromyalgia Patients Receiving tDCS
Official title: Study of the Brain With Optic Functional Neuroimaging in Patients With Chronic Pain Using Transcranial Direct Current Stimulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Fibromyalgia
Chronic Pain
Keywords: Fibromyalgia
Transcranial Direct Current Stimulation
tDCS
Pregabalin
Functional Neuroimaging
Near Infrared Spectroscopy
NIRS
Chronic Pain
Transcranial Magnetic Stimulation
TMS
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2013-07-22
Enrollment: 34
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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in the pressure pain threshold.
timeFrame: 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.
measure: Change in cortical excitability parameters assessed by transcranial magnetic stimulation.
timeFrame: 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.
measure: Changes in motor cortex blood flow assessed by near infrared spectroscopy.
timeFrame: 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 outcomes:
measure: Change in the temperature pain threshold.
timeFrame: 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.
measure: Change in the visual analogue scale for pain to prolonged thermal stimuli.
timeFrame: 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.
measure: Change in average daily pain assessed with the visual analogue scale.
timeFrame: Starting on day 1, each day until Week 12. Total: 84 Evaluations.
measure: Change in the Fibromyalgia Impact Questionnaire.
timeFrame: Day 1 (1 hour before receiving the 1st dose of pregabalin); week 2, week 8 and week 12 after initiating the allocated intervention.
measure: Change in quality of life assessed by the WHOQOL (World Health Organization Quality of Life), reduced form, adapted to Brazilian Portuguese.
timeFrame: Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2, week 8 and week 12 after initiating the allocated intervention.
Other outcomes:
measure: Serum biomarkers levels: The brain derived neurotrophic factor, salivary cortisol, tumor necrosis factor alpha, Interleukin 1, 6 and 10 levels will be measured.
timeFrame: 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.
measure: Level of depressive symptoms.
timeFrame: Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 after initiating the allocated intervention.
measure: Sleep quality.
timeFrame: Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 after initiating the allocated intervention.
measure: Pain catastrophizing thoughts.
timeFrame: Day 1 (1 hour before receiving the 1st dose of pregabalin), week 2 and week 8 after initiating the allocated intervention.
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande do Sul
Study officials:
affiliation: Hospital de Clínicas de Porto Alegre
name: Wolnei Caumo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Arnold LM. Biology and therapy of fibromyalgia. New therapies in fibromyalgia. Arthritis Res Ther. 2006;8(4):212. doi: 10.1186/ar1971.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.