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Investigation of the Efficacy of tDCS in the Treatment of Complex Regional Pain Syndrome (CRPS) Type 1

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ClinicalTrials.gov Identifier: NCT01960400
Recruitment Status : Completed
First Posted : October 10, 2013
Results First Posted : November 16, 2016
Last Update Posted : February 6, 2017
Sponsor:
Information provided by (Responsible Party):
Yannick Tousignant-Laflamme, Université de Sherbrooke

Tracking Information
First Submitted Date  ICMJE September 24, 2013
First Posted Date  ICMJE October 10, 2013
Results First Submitted Date  ICMJE October 28, 2015
Results First Posted Date  ICMJE November 16, 2016
Last Update Posted Date February 6, 2017
Study Start Date  ICMJE April 2013
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
Pain Severity [ Time Frame: Before (T0) and after treatment (6 weeks) (T1) ]
The choice of outcome measures was performed in accordance with Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT) guidelines (Dworkin et al., 2005). All instruments were used before (T0) and after 6 weeks of treatment (T1). The primary outcome measure was pain severity as measured with the Brief pain inventory short-form (BPI-sf) (Poundja et al., 2007). The BPI-sf includes four questions on pain levels, where subjects were asked to rate intensity on a scale of 0 (no pain) to 10 (worst possible pain) for: (1) pain at its worst in the last 24 hours; (2) pain at its least in the last 24 hours; (3) pain on average in the last 24 hours; (4) pain right now. The total score ranges from 0 to 40 (sum of the four subscales). The higher the score, the greater the severity of the pain is severe.
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2013)
The global impression of change [ Time Frame: after end of treatment, 1 and 3 months follow-up ]
Patient Global Impression of Change
Change History Complete list of historical versions of study NCT01960400 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
  • Pain Catastrophizing [ Time Frame: Before (T0) and after treatment (6 weeks) (T1) ]
    The Pain catastrophizing scale (PCS) (Sullivan et al., 1995) was used to evaluate the feelings, thoughts, and emotions related to pain catastrophizing of the patient. The PCS instructions ask participants to reflect on past painful experiences, and to indicate the degree to which they experienced each of 13 thoughts or feelings when experiencing pain, on 5-point scales with the end points (0) not at all and (4) all the time. The PCS yields a total score and three subscale scores assessing rumination, magnification and helplessness. * The scores ranging from 0 to 52 points (sum of the tree subscales), with higher scores representing stronger pain catastrophizing (Sullivan et al., 1995).
  • Kinesiophobia [ Time Frame: Before (T0) and after treatment (6 weeks) (T1) ]
    The Tampa Scale of kinesiophobia (TSK) (Kori et al., 1990) was used to assess fear of movement and injury/(re)injury. The TSK questionnaires consist of 17 items. Each item, composed of a statement, is scored by the patient on a 4-point Likert scale of 1 (strongly disagree) to 4 (strongly agree). The total scores range from 17 to 68, with higher scores representing stronger fear-avoidance beliefs (Clark, Kori, Brockel, 1996).
  • State Anxiety [ Time Frame: Before (T0) and after treatment (6 weeks) (T1) ]
    The State-Trait Anxiety Inventory (STAI) was used to assess the state of anxiety at the moment (Spielberg et al., 1983). The total score is obtained by adding the scores for all 20 questions range from 20 to 80; the higher the result is, the higher is the anxiety about an event.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2013)
  • The clinical pain and global physical function [ Time Frame: after end of treatment, 1 and 3 months follow-up ]
    short form Brief Pain Inventory
  • The perception of the specific function of the upper limb [ Time Frame: after end of treatment, 1 and 3 months follow-up ]
    Disabilities of the Arm, Shoulder and Hand questionnaire on functional disability
  • The perception of the specific function of the lower limb [ Time Frame: after end of treatment, 1 and 3 months follow-up ]
    Lower extremity version of the Impairment Sum Score
  • The impact of pain on health-related quality of life [ Time Frame: after end of treatment, 1 and 3 months follow-up ]
    sf-12
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: October 8, 2013)
Cortical reorganization [ Time Frame: before and 3 months after the treatment ]
Each participant will undergo MRI / fMRI examinations. MRI will enable us to obtain high-resolution images of the various brain structures, which will provide information regarding both cortical thickness and the density of the white and grey matter. fMRI will capture images while the subject is performing a motor activity with the affected limb and will be compared to the opposite (healthy) hemisphere. These images will be reconstructed to highlight the activation sites throughout the brain. These will allow us to measure how brain structures and function are changed following tDCS and GMI treatments, and whether these cortical alterations correlate to the observed clinical changes at post-intervention.
 
Descriptive Information
Brief Title  ICMJE Investigation of the Efficacy of tDCS in the Treatment of Complex Regional Pain Syndrome (CRPS) Type 1
Official Title  ICMJE Investigation of the Efficacy of Transcranial Direct Current Stimulation (tDCS) Added to the Graded Motor Imagery (GMI) in the Treatment of Complex Regional Pain Syndrome (CRPS) Type 1
Brief Summary The efficacy of the current standard non-pharmacological treatments for complex regional pain syndrome (CRPS), a painful syndrome mostly occurring after musculoskeletal trauma, is suboptimal. It thus appears essential to examine new non-pharmacological therapeutic imagery (GMI) - a non-pharmacological approach with the highest level of evidence (level II). As suggested by the most recent clinical guideline 2, a potential solution would be to add an electrotherapeutic procedure - transcranial direct current stimulation (tDCS) - that may prove effective in modulating cortical excitability and reducing the effect of cortical reorganization on pain. Given the positive results previously obtained in patients with neuropathic pain, it is hypothesized that tDCS will prove to be an innovative add-on treatment method for CRPS patients, and help reduce pain and disability.
Detailed Description

Executive summary: The efficacy of the current standard rehabilitation treatments for complex regional pain syndrome (CRPS), a painful syndrome mostly occurring after musculoskeletal trauma, is suboptimal. For instance, the first line of treatment in rehabilitation, progressive motor imagery (GMI), only induces a 50% improvement in symptoms. Although such improvement is interesting, further solutions should be sought to enhance clinical outcomes. It is thus essential to explore new options of therapy. A potential solution to enhance clinical outcomes would be to add an electrotherapeutic procedure, such as transcranial direct current stimulation (tDCS). Given the positive results previously obtained in patients with neuropathic pain, we hypothesize that tDCS will induce functional and structural reorganization in the cortex and lead to better pain relief. The cortical reorganization frequently observed in CRPS patients mainly involves a shrinkage of cortical map of the affected limb on primary and secondary somatosensory cortex. Interestingly, therapies that aim to reverse the cortical reorganization are often associated with a decrease in pain. Therefore, combining GMI and tDCS could lead to added pain relief compared to traditional GMI treatments alone. Furthermore, neuroimaging before and after the procedures could help us explain if and how this is achieved. Objectives: Thus, the primary objective of this research is to study the therapeutic efficacy of tDCS in the treatment of CRPS type 1 in addition to the current best evidence-based rehabilitation treatment, GMI. The second objective is to study, through MRI/fMRI, how brain structures and functions are changed following tDCS and GMI treatments, and whether these changes correlate to clinical changes.

Methodology: To achieve the first objective, we will recruit adults diagnosed with CRPS type 1 via established collaborations with different physicians from our university affiliated hospital. Participants will be randomly allocated into one of the two treatment groups A) experimental group, which will receive the GMI and tDCS stimulation; B) control group, which will receive GMI and sham [placebo] tDCS stimulation. GMI treatment is composed of a three-phase protocol, each lasting two weeks. The GMI treatments will be performed using software and well-established procedures (www.noigroup.com). For its part, the tDCS will be applied for 5 consecutive days during the first 2 weeks of phase 1 and once a week during the 4 other weeks. The anodic (positive) stimulation over the motor cortex (M1) contralateral of the affected limb is sought to modulate cortical excitability and promote pain inhibition and cortical reorganization. Sample size estimates (β:80%,α 5%) show that 15 subjects/group will be necessary.

Anticipated results and impact of the proposed project: This project will allow us to investigate the therapeutic efficacy of an innovative approach to the treatment of CRPS, primarily for the purpose of enhancing the clinical outcomes of GMI. In the event of positive results, we will be able to further examine the therapeutic benefits of this modality in a larger clientele and even in other populations (i.e., patients with chronic low back pain). In addition, our results may contribute to the creation of a clinical practice guide, since there currently is insufficient evidence-based data to establish guidelines regarding the non-pharmacological treatment of CRPS. Finally, MRI/fMRI analysis will help us to capture the phenomenon of tDCS-driven cortical reorganization.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Reflex Sympathetic Dystrophy
Intervention  ICMJE
  • Device: transcranial direct current stimulation (tDCS) (active or placebo)
    TDCS was delivered according to the method described by Fregni et al. (2006) and the safety parameters related to tDCS application were respected (DaSilva et al., 2011). Direct current was delivered using a battery-driven constant current stimulator coupled to saline-soaked (0.9% NaCl) sponge electrodes (5 X 7 cm). Anodal stimulation was delivered over the M1; the anode was placed over C3 or C4 position in the 10/20 system for the EEG electrode position, contralateral to the affected limb, and the cathode over the opposite supraorbital area (i.e. ipsilateral to the affected limb). In the laboratory, a constant current of an intensity of 2 mA was applied for 20 min/day X 5 consecutive days during the first and the second weeks of GMI. To help maintain the potential effects of the neurostimulation, the tDCS was also applied simultaneously with GMI once a week during the 2 other phases until the end of the six weeks GMI program, for a total of 14 treatment sessions.
    Other Name: Transcranial direct current stimulation
  • Device: Graded motor imagery (GMI)
    The treatment was performed using a software (Recognise™ online) provided by NOI group (http://www.noigroup.com/recognise). As an alternative to the software (for patients without an internet access), the patient could do the exercises with a Recognise™ Flash Cards set consists of 25 left and 25 right matching images (upper limb or lower limb). Using standardized procedures, inspired from the randomized controlled trial conducted by Moseley (2004, 2006), the participants performed the therapy at home, 10 minutes per session, 3x/day, 6 days/week, using the computer software and a mirror box (Lagueux et al., 2012).
Study Arms  ICMJE
  • Active Comparator: GMI + tDCS
    Graded motor imagery (GMI) + tDCS
    Interventions:
    • Device: transcranial direct current stimulation (tDCS) (active or placebo)
    • Device: Graded motor imagery (GMI)
  • Placebo Comparator: GMI + sham TDCS
    Graded motor imagery (GMI) + sham tDCS
    Interventions:
    • Device: transcranial direct current stimulation (tDCS) (active or placebo)
    • Device: Graded motor imagery (GMI)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2016)
22
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2013)
28
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults diagnosed with CRPS type 1, based on Bruehl's diagnostic criteria for research.

Exclusion Criteria:

  • Other painful conditions;
  • Central nervous system disease;
  • Other upper limb conditions;
  • Diagnosis of psychiatric condition;
  • Dyslexia and/or severe visual impairment;
  • Presence of contraindication of tDCS (brain implant, history of severe cranial trauma, severe or frequent headaches, chronic skin conditions);
  • Sympathetic blocks for less than one month;
  • Pregnancy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01960400
Other Study ID Numbers  ICMJE 12-116
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yannick Tousignant-Laflamme, Université de Sherbrooke
Study Sponsor  ICMJE Université de Sherbrooke
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yannick Tousignant-Laflamme, PhD Université de Sherbrooke
Principal Investigator: Patricia Bourgault, PhD Université de Sherbrooke
PRS Account Université de Sherbrooke
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP