Augmentation of EMDR With tDCS in the Treatment of Fibromyalgia

Official title

Augmentation of EMDR With Transcranial Direct Current Stimulation (tDCS) in the Treatment of Fibromyalgia: a Double-blind Randomized Controlled Trial

Overview

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 transcranial Direct Current Stimulation (tDCS), 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 96 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 tDCS or EMDR plus sham-tDCS, or Treatment as Usual (TAU). Therapists, raters, and patients will be kept blind to tDCS 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 tDCS enhances this effect, which will be superior to tDCS-sham.

Detailed description

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 Barcelona, whether a trauma-oriented therapy, Eye Movement Desensitization Reprocessing (EMDR), in combination with a non-invasive brain stimulation technique, transcranial Direct Current Stimulation (tDCS), can improve typical FM symptoms.

Outcomes

Primary outcomes:

1. To test whether EMDR plus tDCS or EMDR plus sham-tDCS in comparison to TAU group, improve pain intensity, depressive and anxious symptoms and trauma associated symptoms after therapy and follow-up. 2. To test whether an improvement in pain intensity, depressive and anxious symptoms and trauma associated symptoms can be augmented by simultaneous tDCS comparing EMDR plus tDCS with EMDR plus sham-tDCS after the intervention and whether this is maintained at the follow-up visit.

Secondary outcomes: 3. To test whether the EMDR plus tDCS or EMDR plus sham-tDCS in comparison 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 Rheumatology Department of the Parc de Salut Mar responsible for patient recruitment, and the Cognitive Neuro-Lab of the Universitat Oberta de Catalunya for guidance and council on tDCS use.

Design

Within a double-blind randomized controlled design, patients will be randomized to one of the following three treatment arms:

EMDR with tDCS (20 sessions) vs EMDR with sham-tDCS (20 sessions) vs TAU. Psychotherapists, raters, and patients will be kept blind for tDCS treatment conditions until the end of the trial.

Participants

The patient sample will consist of 96 females fulfilling the 2016 American College of Rheumatology criteria for FM based on clinical interview (Wolfe et al, 2010).

Interventions

* EMDR therapy * transcranial Direct Current Stimulation (tDCS) * Treatment as Usual

Randomizations

Participants were randomly assigned to one of the three study groups using REDCap's stratified randomization module to ensure balanced allocation in terms of Revised Fibromyalgia Impact Questionnaire (FIQ-R) score and education level. When a new participant is enrolled, REDCap identifies their stratum based on the data for these two variables, then it assigns them to a study arm using block randomization within that stratum, favoring the arm with the fewest current assignments to maintain balance. The allocation sequence is concealed from outcome raters until participants have finished the trial. This randomization module enforces balance by prioritizing equal group sizes within strata, even with uneven stratum sizes, it provides real-time adaptations by adjusting assignments dynamically as participants enroll and it logs all randomization events for reproducibility purposes.

Computation of sample size

The main tests of the study will consist of assessing whether patients assigned to EMDR show different levels in the pain intensity variable using a standard formula for two-tailed t-tests. The total sample size required to detect large to very large effect size differences (Cohen's d ≥ 1) between three groups with a significance level of 0.05 and statistical power of 80% is 28. Assuming 15% dropouts, we will aim to randomize 96 patients, meaning 32 per group.

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.

Interventions

• Behavioral Eye Movement Desensitization and Reprocessing therapy
  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-c
• Other transcranial Direct Current Stimulation
  tDCS represents a promising intervention option, given its capacity to modulate cerebral excitability in a simple, safe manner. F3 anodal; Fp1, F7, Fc5, AF3, Fc1, Fz, 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 2mA tDCS for 20 minutes applied immediately before EMDR sessions. The same protocol and montage will be used for sham stimulation.

Primary outcome measures

• Change in severity and in pain intensity as measured by the Visual Analogue Scale (VAS) [Time frame: Change from baseline to visits at 6 and 12 months]
• Change in physical impairment due to FM assessed by The Revised Fibromyalgia Impact Questionnaire (FIQ-R) [Time frame: Change from baseline to visits at 6 and 12 months]
• Change in catastrophic thinking related to pain experiences assessed by the Pain Catastrophizing Scale (PCS) [Time frame: Change from baseline to visits at 6 and 12 months]
• Change in the impact of fatigue as assessed by the Brief Fatigue Inventory (BFI) [Time frame: Change from baseline to visits at 6 and 12 months]
• PTSD diagnosis assessed by the Global Evaluation of Posttraumatic Stress (EGEP-5) [Time frame: Change from baseline to 6 and 12 months]
• Complex PTSD diagnosis assessed by The International Trauma Questionnaire (ITQ) [Time frame: Measure at baseline]
• Change in PTSD symptoms as measured by the Posttraumatic Stress Disorder Checklist (PCL-5) [Time frame: Change from baseline to visits at 6 and 12 months]
• Change in subjective perceived distress assessed by Subjective unit of distress (SUD) [Time frame: Change from baseline to visits at 6 and 12 months]
• Quantifying childhood trauma assessed by The Childhood Trauma Questionnaire (CTQ) [Time frame: Measure at baseline.]
• Assessing lifetime trauma with the Timeline of traumatic experiences [Time frame: Measure at baseline]

Secondary outcome measures (6)

• Change in subjective wellbeing measured with the Satisfaction With Life Scale. [Time frame: Change from baseline to visits at 6 and 12 months]
• Change in insomnia symptoms assessed with the Athens Insomnia Scale. [Time frame: Change from baseline to visits at 6 and 12 months]
• Change in Self-care assessed with The González self-care scale. [Time frame: Change from baseline to 6 and 12 months.]
• Change in emotion regulation assessed with The Emotion-Regulation Skills Questionnaire (ERSQ). [Time frame: Change from baseline to 6 and 12 months.]
• Change in self-esteem assessed with The Rosenberg Self-Esteem Scale (RSE). [Time frame: Change from baseline to 6 and 12 months.]
• Change in cognitive function assessed with The Screen for Cognitive Impairment in Psychiatry (SCIP). [Time frame: Change from baseline to 6 and 12 months.]

Eligibility criteria

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 in the past two years
• 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
• Skin sensitivity diseases (psoriasis, eczema, dermatitis, etc.)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Spain · 1 center

• Centre Forum (Parc de Salut Mar) — Barcelona

Publications

• Font Gaya T, Bordoy Ferrer C, Juan Mas A, Seoane-Mato D, Alvarez Reyes F, Delgado Sanchez M, Martinez Dubois C, Sanchez-Fernandez SA, Marena Rojas Vargas L, Garcia Morales PV, Olive A, Rubio Munoz P, Larrosa M, Navarro Ricos N, Sanchez-Piedra C, Diaz-Gonzalez F, Bustabad-Reyes S; Working Group Proyecto EPISER2016. Prevalence of fibromyalgia and associated factors in Spain. Clin Exp Rheumatol. 2020 PMID 31928589
• Benor D, Rossiter-Thornton J, Toussaint L. A Randomized, Controlled Trial of Wholistic Hybrid Derived From Eye Movement Desensitization and Reprocessing and Emotional Freedom Technique (WHEE) for Self-Treatment of Pain, Depression, and Anxiety in Chronic Pain Patients. J Evid Based Complementary Altern Med. 2017 Apr;22(2):268-277. doi: 10.1177/2156587216659400. Epub 2016 Jul 20. PMID 27432773
• Bernardy K, Klose P, Busch AJ, Choy EH, Hauser W. Cognitive behavioural therapies for fibromyalgia. Cochrane Database Syst Rev. 2013 Sep 10;2013(9):CD009796. doi: 10.1002/14651858.CD009796.pub2. PMID 24018611
• Borchers AT, Gershwin ME. Fibromyalgia: A Critical and Comprehensive Review. Clin Rev Allergy Immunol. 2015 Oct;49(2):100-51. doi: 10.1007/s12016-015-8509-4. PMID 26445775
• Burke NN, Finn DP, McGuire BE, Roche M. Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms. J Neurosci Res. 2017 Jun;95(6):1257-1270. doi: 10.1002/jnr.23802. Epub 2016 Jul 12. PMID 27402412
• Cohen H, Neumann L, Haiman Y, Matar MA, Press J, Buskila D. Prevalence of post-traumatic stress disorder in fibromyalgia patients: overlapping syndromes or post-traumatic fibromyalgia syndrome? Semin Arthritis Rheum. 2002 Aug;32(1):38-50. doi: 10.1053/sarh.2002.33719. PMID 12219319
• Collado A, Gomez E, Coscolla R, Sunyol R, Sole E, Rivera J, Altarriba E, Carbonell J, Castells X. Work, family and social environment in patients with Fibromyalgia in Spain: an epidemiological study: EPIFFAC study. BMC Health Serv Res. 2014 Nov 11;14:513. doi: 10.1186/s12913-014-0513-5. PMID 25385047
• Crettaz B, Marziniak M, Willeke P, Young P, Hellhammer D, Stumpf A, Burgmer M. Stress-induced allodynia--evidence of increased pain sensitivity in healthy humans and patients with chronic pain after experimentally induced psychosocial stress. PLoS One. 2013 Aug 7;8(8):e69460. doi: 10.1371/journal.pone.0069460. eCollection 2013. PMID 23950894

Identifiers

NCT: NCT04084795 · 2019/8772/I

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗