Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol

Introduction Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventi...

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Main Authors: Luis Castelo-Branco, Elif Uygur Kucukseymen, Dante Duarte, Mirret M El-Hagrassy, Camila Bonin Pinto, Muhammed Enes Gunduz, Alejandra Cardenas-Rojas, Kevin Pacheco-Barrios, Yiling Yang, Paola Gonzalez-Mego, Anayali Estudillo-Guerra, Ludmilla Candido-Santos, Ines Mesia-Toledo, Haley Rafferty, Wolnei Caumo, Felipe Fregni
Format: Article
Language:English
Published: BMJ Publishing Group 2019-10-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/10/e032710.full
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author Luis Castelo-Branco
Elif Uygur Kucukseymen
Dante Duarte
Mirret M El-Hagrassy
Camila Bonin Pinto
Muhammed Enes Gunduz
Alejandra Cardenas-Rojas
Kevin Pacheco-Barrios
Yiling Yang
Paola Gonzalez-Mego
Anayali Estudillo-Guerra
Ludmilla Candido-Santos
Ines Mesia-Toledo
Haley Rafferty
Wolnei Caumo
Felipe Fregni
author_facet Luis Castelo-Branco
Elif Uygur Kucukseymen
Dante Duarte
Mirret M El-Hagrassy
Camila Bonin Pinto
Muhammed Enes Gunduz
Alejandra Cardenas-Rojas
Kevin Pacheco-Barrios
Yiling Yang
Paola Gonzalez-Mego
Anayali Estudillo-Guerra
Ludmilla Candido-Santos
Ines Mesia-Toledo
Haley Rafferty
Wolnei Caumo
Felipe Fregni
author_sort Luis Castelo-Branco
collection DOAJ
description Introduction Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control.Methods and analysis A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)—primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study—CPM and TSPS—and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables.Ethics and dissemination This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications.Trial registration number NCT03371225.
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spelling doaj-art-2e4171b092bb4064821eee366c10b6a12025-08-20T02:37:58ZengBMJ Publishing GroupBMJ Open2044-60552019-10-0191010.1136/bmjopen-2019-032710Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocolLuis Castelo-Branco0Elif Uygur Kucukseymen1Dante Duarte2Mirret M El-Hagrassy3Camila Bonin Pinto4Muhammed Enes Gunduz5Alejandra Cardenas-Rojas6Kevin Pacheco-Barrios7Yiling Yang8Paola Gonzalez-Mego9Anayali Estudillo-Guerra10Ludmilla Candido-Santos11Ines Mesia-Toledo12Haley Rafferty13Wolnei Caumo14Felipe Fregni15Neuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USANeuromodulation Center/Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USALaboratory of Pain & Neuromodulation, Hospital de Clinicas de Porto Alegre da Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilDepartment of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Boston, Massachusetts, USAIntroduction Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control.Methods and analysis A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)—primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study—CPM and TSPS—and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables.Ethics and dissemination This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications.Trial registration number NCT03371225.https://bmjopen.bmj.com/content/9/10/e032710.full
spellingShingle Luis Castelo-Branco
Elif Uygur Kucukseymen
Dante Duarte
Mirret M El-Hagrassy
Camila Bonin Pinto
Muhammed Enes Gunduz
Alejandra Cardenas-Rojas
Kevin Pacheco-Barrios
Yiling Yang
Paola Gonzalez-Mego
Anayali Estudillo-Guerra
Ludmilla Candido-Santos
Ines Mesia-Toledo
Haley Rafferty
Wolnei Caumo
Felipe Fregni
Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol
BMJ Open
title Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol
title_full Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol
title_fullStr Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol
title_full_unstemmed Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol
title_short Optimised transcranial direct current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol
title_sort optimised transcranial direct current stimulation tdcs for fibromyalgia targeting the endogenous pain control system a randomised double blind factorial clinical trial protocol
url https://bmjopen.bmj.com/content/9/10/e032710.full
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