Augmentation of EMDR With MtCS in the Treatment of Fibromyalgia

Study Overview
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Brief Summary
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Fibromyalgia (FM) is a generalized, widespread chronic pain disorder and has an estimated prevalence of 2%-4% in the general population. Current pharmacological and psychological interventions frequently produce limited benefits in FM patients. Due to FM's strong association with psychological trauma causing neurobiological alterations in stress response, a trauma-focused psychotherapy is an innovative alternative treatment option. Eye Movement Desensitization and Reprocessing (EMDR) has been recognized by the World Health Organization as a first-line therapeutic tool for post-traumatic stress disorder and first evidence suggests that it is also beneficial for patients with FM. Given the complex etiology of FM, a combination of psychotherapy with other treatment options can maximize a potential therapeutic success. A possible candidate herby is Multifocal transcranial Current Stimulation (MtCS), a non-invasive stimulation technique, which can modify neural activities related to pain and which has shown short-term positive effects on chronic pain and quality of life in FM patients. The patient sample will consist of 45 female patients meeting 2016 American College of Rheumatology criteria for FM based on a clinical interview. They will be randomized to 20 sessions of EMDR plus MtCS or EMDR plus sham-MtCS, or Treatment as Usual (TAU). Therapists, raters, and patients will be kept blind to MtCS treatment conditions. Evaluations will be at baseline, post treatment at 6 months, and follow-up at 12 months. Hypotheses are that EMDR improves pain intensity and clinical symptoms at short and long-term, and that MtCS enhances this effect, which will be superior to MtCS-sham.

Detailed Description
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Fibromyalgia (FM) affects 2-4% of the general population with typical symptoms such as generalized and widespread pain, sleep disturbances, problems in memory and attention, anxiety and depression. Pharmacological treatment and psychotherapeutic interventions have produced limited effects so far. Interestingly, lifetime psychosocial adversities are substantially elevated in FM but no interventions are currently offered. Given the complex etiology of FM, combining a psychotherapy with other treatment options can maximize the potential benefit of this intervention. The investigators will test in a marginalized catchment area in Barcelona, whether a trauma-oriented therapy, Eye Movement Desensitization Reprocessing (EMDR), in combination with a non-invasive brain stimulation technique, Multifocal transcranial Current Stimulation (MtCS), can improve typical FM symptoms. Outcomes Primary outcomes: To test whether EMDR plus MtCS or EMDR plus sham-MtCS in comparison to TAU group, improve pain intensity, depressive and anxious symptoms and trauma associated symptoms after therapy and follow-up. To test whether an improvement in pain intensity, depressive and anxious symptoms and trauma associated symptoms can be augmented by simultaneous MtCS comparing EMDR plus MtCS with EMDR plus sham-MtCS after the intervention and whether this is maintained at the follow-up visit. Secondary outcomes: To test whether the EMDR plus MtCS or EMDR plus sham-MtCS incomparison to TAU group, improves more in subjective wellbeing after the treatment, and whether this is maintained at the follow-up visit. Indicators to monitor clinical changes will be performed via various standard self- and hetero-applied scales by blind-to-treatment raters and information provided by patients and the medical chart IT system of our catchment area at baseline (visit 1), post treatment at 6 months (visit 2), and follow-up evaluation at 12 months (visit 3). This multicenter collaborative project will involve the participation of the Psychiatric Department of the Parc de Salut Mar responsible for coordinating the study, the Rheumatologist Department of the Parc de Salut Mar responsible for patient recruitment, the Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) responsible for randomization and data base management, and the Cognitive Neuro-Lab responsible for the MtCS stimulation. Design Within a double-blind randomized controlled design, patients will be randomized to one of the following three treatment arms: EMDR with MtCS (20 sessions) vs EMDR with sham-MtCS (20 sessions) vs TAU. Psychotherapists, raters, and patients will be kept blind for MtCS treatment conditions until the end of the trial. Participants The patient sample will consist of 45 females fulfilling the 2016 American College of Rheumatology criteria for FM based on clinical interview (Wolfe et al, 2010). Interventions EMDR therapy Multifocal transcranial Current Stimulation (MtCS) Treatment as Usual Randomizations The main analysis will be the comparison between patients assigned to EMDR vs not assigned to EMDR, and the secondary analysis will be, among patients assign to EMDR, the comparison between patients with FM assigned to active MtCS vs patients with FM assigned to sham MtCS. Therefore, the investigators will not randomly assign the individuals to one of the three arms but, rather, will randomize patients meeting the inclusion criteria twice: they will first randomize them to EMDR vs non-EMDR, and then will randomize those in the EMDR group to active MtCS or sham MtCS. For the sake of brevity, the investigators describe here only the randomization to EMDR vs non-EMDR, because the randomization to active MtCS vs. sham MtCS is identical. The first two patients will be randomly allocated to EMDR with p=2/3. For each subsequent patient, the following biased coin algorithm will be applied. If a group includes at least two more patients than it would have to have to maintain the ratio 2 EMDR / 1 control, the patient will be randomly assigned to the other group with p=0.6. Otherwise, the researchers will simulate that the new patient is allocated to EMDR and calculate the between-group standardized difference in pain intensity variable, will then simulate that the new patient is allocated to non-EMDR and recalculate the difference, and finally randomly allocate the patient to the group associated to the smallest difference with p=0.6. This strategy decreases prognostic imbalances between groups because it decreases differences in potential confounders but it still includes randomization. Computation of sample size The main tests of the study will consist in assessing whether patients assigned to EMDR show different levels of pain intensity variable using standard formula, the total sample size required to detect large to very large effect size differences (Cohen's d ≥ 1) between two groups with a significance level of 0.05 is 13 and 26. Assuming 15% dropouts, the researchers will aim to randomize 45 patients, i.e. 15 and 30 per arm. Statistical Analysis The distribution of socio-demographic and clinical characteristics between groups at baseline will be summarized using descriptive statistics. The change in clinical and functional variables from the baseline evaluation to post intervention will be analyzed using linear model t-tests, including as regressors of no interest the potential confounders (age, pain score, anxiety and depression severity, and number of years in education). The statistical software used for the analysis will be the latest available version of R. The investigators will conduct an intention to treat (ITT) analysis, and will use the Last Observation Carried Forward (LOCF) method for losses at follow-up.

Official Title
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Augmentation of EMDR With Multifocal Transcranial Current Stimulation in the Treatment of Fibromyalgia: a Randomized Controlled Trial

Conditions
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Fibromyalgia, Psychological Trauma, Depressive Symptoms, Anxiety

Intervention / Treatment
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* Behavioral: Eye Movement Desensitization and Reprocessing therapy
* Other: Multifocal transcranial Current Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 70 years old Mean pain score of at least 4 on the visual analog scale (VAS) in the two weeks preceding the clinical trial Presence of one or more traumatic events causing current trauma-related symptoms Current clinical symptoms of depression and/or anxiety 2 weeks of stable medication Exclusion Criteria: Comorbid autoimmune or chronic inflammatory disease Neurological or serious medical diseases Bipolar disorder, schizoaffective disorder and schizophrenia Suicidal ideation Previous EMDR therapy Substance abuse/dependency within 1 month prior to participation (except for nicotine abuse/dependency), Pending FM-related litigation or disability Metallic implants in the head Positive test for pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EMDR plus MtCS<br>MtCS stimulation will consist of 1mA MtDCS for 20 minutes applied immediately before EMDR sessions. | Behavioral: Eye Movement Desensitization and Reprocessing therapy<br>* EMDR is a psychotherapeutic approach using a standardized 8-phase protocol to alleviate the distress associated with traumatic memories, facilitating the access to and processing of traumatic memories. Patients will receive 20 individual EMDR sessions of 60 minutes each using the standard protocol, as well as a specific pain protocol and the fibromyalgia protocol. EMDR is an integrative psychotherapy that uses standardized protocols and elements of cognitive-behavioral, interpersonal, and body-centered therapies, as well as dual stimulation (e.g., side-to-side eye movements). The current standard protocol includes eight phases: Patient history. Patient preparation. Patient assessment. Memory desensitization. Installing the positive cognition. Body scan. Closure. Reevaluation.<br>* Other names: EMDR;Other: Multifocal transcranial Current Stimulation<br>* MtCS represents a promising intervention option, given its capacity to modulate cerebral excitability in a simple, safe manner. F3 anodal; AF3, FC1, FC3, FC5, F5, return montage will be used with the anode over the left DLPFC. Half of the patients will receive active stimulation and the other half sham stimulation. Active stimulation will consist of 1mA MtDCS for 20 minutes applied immediately before EMDR sessions. The same protocol and montage will be used for sham stimulation.<br>* Other names: MtCS;|
| Placebo Comparator: EMDR plus sham-MtCS<br>Sham stimulation will consist of inactive MtDCS for 20 minutes applied immediately before EMDR sessions | Behavioral: Eye Movement Desensitization and Reprocessing therapy<br>* EMDR is a psychotherapeutic approach using a standardized 8-phase protocol to alleviate the distress associated with traumatic memories, facilitating the access to and processing of traumatic memories. Patients will receive 20 individual EMDR sessions of 60 minutes each using the standard protocol, as well as a specific pain protocol and the fibromyalgia protocol. EMDR is an integrative psychotherapy that uses standardized protocols and elements of cognitive-behavioral, interpersonal, and body-centered therapies, as well as dual stimulation (e.g., side-to-side eye movements). The current standard protocol includes eight phases: Patient history. Patient preparation. Patient assessment. Memory desensitization. Installing the positive cognition. Body scan. Closure. Reevaluation.<br>* Other names: EMDR;|
| No Intervention: Treatment as Usual<br>Patients in this condition will not receive EMDR nor MtCS sessions, and will continue to attend their regular visits with rheumatology and psychiatry. The patients from the TAU group will have the choice to attend 10 sessions of EMDR group therapy when the research project finishes. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain assessed with the Visual Analogic Scale Questionnaire. | Severity and changes in pain intensity will be assessed with the Visual Analogic Scale (rated in a continuum from 0 to 10). | Change from baseline to visits at 6 and 12 months | 
| Change in pain assessed with the Pain Dissability Index. | Severity and changes in pain intensity will be assessed with the Pain Disability Index (7 items rated from 0 to 10, making a total score from 0 to 70). | Change from baseline to visits at 6 and 12 months | 
| Change in pain assessed with the Fibromyalgia Impact Questionnaire. | Severity and changes in pain intensity will be assessed with the Fibromyalgia Impact Questionnaire (the first items is rated from 0 to 4, the second from 0 to 7 and the third from 0 to 5; whereas the other 7 items are rated from 0 to 10, with a cut-off score of 50). | Change from baseline to visits at 6 and 12 months | 
| Change in depressive symptoms assessed by with the Hospital Anxiety and Depression Scale | Severity and changes in depressive symptoms will be evaluated with the Hospital Anxiety and Depression Scale. Items are rated on a 4-point Likert scale from 0 and 3, yielding a total score ranging from 0 to 21 and a cut-off score of 8 indicating probable clinical symptoms. | Change from baseline to visits at 6 and 12 months | 
| Change in anxious symptoms evaluated with the Hospital Anxiety and Depression Scale. | Severity and changes in anxious symptoms will be evaluated with the Hospital Anxiety and Depression Scale. Items are rated on a 4-point Likert scale from 0 and 3, yielding a total score ranging from 0 to 21 and a cut-off score of 8 indicating probable clinical symptoms. | Change from baseline to visits at 6 and 12 months | 
| Change in trauma associated symptoms assessed with the Impact of Events Scale-Revised. | Psychological trauma will be evaluated using the Impact of Events Scale-Revised. This scale consists in 22-item to determine frequency and impact of posttraumatic symptoms experienced, with subscales of intrusion, avoidance and hyperarousal, each scored on a 5-point Likert scale, yielding a score for each subscale and a total score. This scale has a scoring range of 0 to 88. On this test, scores that exceed 24 can be quite meaningful. High scores have the following associations: 24 or more PTSD is a clinical concern. Those with scores this high who do not have full PTSD will have partial PTSD or at least some of the symptoms; 33 and above represents the best cutoff for a probable diagnosis of PTSD; 37 or more this is high enough to suppress your immune system's functioning (even 10 years after an impact event). | Change from baseline to visits at 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in subjective wellbeing measured with the Satisfaction With Life Scale. | The improvement of subjective wellbeing will be evaluated using the Satisfaction With Life Scale. This scale is completed by 5 items rated from 1 (totally agree) to 5 (totally disagree), with a maximum score of 25. | Change from baseline to visits at 6 and 12 months | 
| Change in insomnia symptoms assessed with the Athens Insomnia Scale. | The improvement of insomnia symptoms will be evaluated using the Athens Insomnia Scale. This scale is completed by 8 items rated from 0 to 3, with a maximum score of 24. | Change from baseline to visits at 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibromyalgia, Psychological trauma, Posttraumatic stress disorder, Major depressive disorder, Anxiety disorder, Eye Movement Desensitization and Reprocessing, Multifocal transcranial Current Stimulation