Clinical trial NCT04084795: Augmentation of EMDR With tDCS in the Treatment of Fibromyalgia
Official title: Augmentation of EMDR With Transcranial Direct Current Stimulation in the Treatment of Fibromyalgia: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Fibromyalgia
Psychological Trauma
Depressive Symptoms
Anxiety
Keywords: Fibromyalgia
Psychological trauma
Posttraumatic stress disorder
Major depressive disorder
Anxiety disorder
Eye Movement Desensitization and Reprocessing
Multifocal transcranial Current Stimulation
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: Universitat Oberta de Catalunya
name: Institut d'Investigacions Biomèdiques August Pi i Sunyer
First posted: 2019-09-10
Enrollment: 96
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 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 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 tDCS or EMDR plus sham-tDCS, 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 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 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 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 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.

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
* 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

Primary outcomes:
measure: Change in pain assessed with the Visual Analogic Scale Questionnaire.
timeFrame: Change from baseline to visits at 6 and 12 months
measure: Change in pain assessed with the Pain Dissability Index.
timeFrame: Change from baseline to visits at 6 and 12 months
measure: Change in pain assessed with the Fibromyalgia Impact Questionnaire.
timeFrame: Change from baseline to visits at 6 and 12 months
measure: Change in depressive symptoms assessed by with the Hospital Anxiety and Depression Scale
timeFrame: Change from baseline to visits at 6 and 12 months
measure: Change in anxious symptoms evaluated with the Hospital Anxiety and Depression Scale.
timeFrame: Change from baseline to visits at 6 and 12 months
measure: Change in trauma associated symptoms assessed with the Impact of Events Scale-Revised.
timeFrame: Change from baseline to visits at 6 and 12 months
Secondary outcomes:
measure: Change in subjective wellbeing measured with the Satisfaction With Life Scale.
timeFrame: Change from baseline to visits at 6 and 12 months
measure: Change in insomnia symptoms assessed with the Athens Insomnia Scale.
timeFrame: Change from baseline to visits at 6 and 12 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Centre Forum (Parc de Salut Mar)
state: Catalunya
Study officials:
affiliation: Parc de Salut Mar
name: Benedikt L. Amann, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Hampstead BM, Briceno EM, Mascaro N, Mourdoukoutas A, Bikson M. Current Status of Transcranial Direct Current Stimulation in Posttraumatic Stress and Other Anxiety Disorders. Curr Behav Neurosci Rep. 2016 Jun;3(2):95-101. doi: 10.1007/s40473-016-0070-9. Epub 2016 Mar 28.
citation: Lumley MA, Schubiner H, Lockhart NA, Kidwell KM, Harte SE, Clauw DJ, Williams DA. Emotional awareness and expression therapy, cognitive behavioral therapy, and education for fibromyalgia: a cluster-randomized controlled trial. Pain. 2017 Dec;158(12):2354-2363. doi: 10.1097/j.pain.0000000000001036.
citation: O'Connell NE, Marston L, Spencer S, DeSouza LH, Wand BM. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2018 Mar 16;3(3):CD008208. doi: 10.1002/14651858.CD008208.pub4.
citation: Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10. doi: 10.1002/acr.20140.
citation: Yavne Y, Amital D, Watad A, Tiosano S, Amital H. A systematic review of precipitating physical and psychological traumatic events in the development of fibromyalgia. Semin Arthritis Rheum. 2018 Aug;48(1):121-133. doi: 10.1016/j.semarthrit.2017.12.011. Epub 2018 Jan 10.
citation: Gardoki-Souto I, Martin de la Torre O, Hogg B, Redolar-Ripoll D, Valiente-Gomez A, Martinez Sadurni L, Blanch JM, Lupo W, Perez V, Radua J, Amann BL, Moreno-Alcazar A. Augmentation of EMDR with multifocal transcranial current stimulation (MtCS) in the treatment of fibromyalgia: study protocol of a double-blind randomized controlled exploratory and pragmatic trial. Trials. 2021 Jan 29;22(1):104. doi: 10.1186/s13063-021-05042-w.