Cost-utility and Biological Underpinnings of MBSR in Fibromyalgia Syndrome

Study Overview
=================
Brief Summary
-----------------
Purpose: Fibromyalgia syndrome (FMS) is a disabling condition mainly characterized by chronic widespread pain, disturbed sleep, fatigue, and distress. The estimated overall prevalence of FMS in Europe is 2.9% and it incurs in high personal, social and healthcare costs. Available treatments in FMS are not curative and there is some evidence of positive effects of mindfulness-based stress reduction (MBSR) in patients with chronic pain and FMS. Nevertheless, although promising, the positive findings obtained in previous studies implementing mindfulness-based interventions in patients with FMS have to be interpreted with caution due to important methodological limitations (e.g. absence of randomization, high attrition rates, or small sample sizes). Therefore, further research in larger studies using more adequate methodologies is warranted. Furthermore, little is known about putative neurobiological processes underpinning the effects of mindfulness training in patients with chronic pain. Aims: The aim of this randomized, controlled trial (RCT) is two-fold: firstly, to assess the effectiveness and cost-utility of MBSR added to treatment as usual (TAU); and secondly, to evaluate the effects of the compared interventions on neurobiological parameters. Specifically, MBSR will be compared to an active control which was previously reported as a cost-effective intervention (TAU + FibroQol psycho-educational program; Luciano et al., 2013) and also vs. TAU alone (in a 12-month follow-up RCT). Brain structure and function of pain-relevant areas and levels of inflammation markers (cytokines) will be assessed pre-post interventions in half of the study participants. Methods: Design: RCT with three arms: TAU + MBSR, TAU + FibroQoL and TAU. Sample: 180 adults with FMS according to the ACR 1990 criteria (N=60 for each study arm) will be recruited from from the Parc Sanitari Sant Joan de Déu Rheumatology Service, Sant Boi de Llobregat, Spain. Half of the participants will be randomly selected to participate in the neurobiological pre-post evaluation (N= 30 each group). All patients will be assessed at baseline, post-intervention and 12-month follow-up for clinical variables, prep-post intervention for biomarkers study, and baseline and 12-month follow-up for cost-related variables.

Detailed Description
-----------------
Detailed description of the study protocol has been published elsewhere (in an open-access journal): http://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-016-1068-2

Official Title
-----------------
Cost-utility and Biological Underpinnings of Mindfulness-Based Stress Reduction (MBSR) in Fibromyalgia Syndrome: A Three-arm Randomized, Controlled Trial (EUDAIMON Project)

Conditions
-----------------
Fibromyalgia Syndrome

Intervention / Treatment
-----------------
* Behavioral: MBSR
* Behavioral: FibroQol
* Drug: TAU


Participation Criteria
=================
Eligibility Criteria
-----------------
General Inclusion Criteria: Patients of both genders between 18-65 years old. Verified diagnosis of FMS according to the American College of Rheumatology criteria (ACR 1990). Ability to understand Spanish language. Written informed consent. General Exclusion Criteria: Participation in other clinical trials Cognitive impairment according to MINI (total score ≤ 24) Receiving psychological treatment during the last or the current year Previous experience with meditation or mind-body therapies. Physical/psychiatric comorbidity that interferes with treatment (any severe medical illness, psychotic symptoms, substance abuse). Not being able to attend to group sessions. Being involved in ongoing litigation relating to the FMS. Additional Inclusion Criteria for the biomarkers sub-study (90 participants in total): Female gender Right-handed Additional Exclusion Criteria for the biomarkers sub-study: Neoplastic illnesses (diagnosed from the medical history), infection, cardiopulmonary, vascular or other internal medical conditions Use of oral or local corticosteroids or anti-cytokine therapy Needle-phobia Impossibility of being scanned in MRI (due to agoraphobia, metal implants, pace-marker…) BMI> 36kg/m2 or >110Kg Consuming > 8 caffeine units per day Smoking > 5 cigarettes per day Acute pain not related to the FMS at the day of biomarkers evaluation Being pregnant or breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mindfulness-Based Stress Reduction<br>Mindfulness-Based Stress Reduction (MBSR) The MBSR consists in eight 2-h group sessions and an all-day mindfulness retreat, and offers intensive and structured training in mindfulness meditation to help patients to relate to their physical and psychological conditions in more accepting and nonjudgmental ways. Participants will be encouraged to engage in home mindfulness practices. Sessions will be lead by 4 MBSR accredited instructors. | Behavioral: MBSR<br>* Session 1: Recognising the present moment Session 2: Engaging with the breath Session 3: Practice, practice, practice Session 4: Stress and the flow of emotions Session 5: Stress and thoughts: finding another place to stand Session 6: Interpersonal mindfulness / mindful communication. Session 7: Applying mindfulness Session 8: Making mindfulness a part of your life<br>Drug: TAU<br>* In Spain the treatment as usual provided in FMS is mainly pharmacological and adjusted to the symptomatic profile of the patient. Counselling about aerobic exercise adjusted to patients' physical limitations is usually also provided.<br>* Other names: Usual care;|
| Active Comparator: Psycho-educational Program<br>Psycho-educational Program (FibroQol) It consists of eight 2-h group sessions including information about FMS (4 sessions) based on a consensus document of the Health Department of Catalonia + autogenic relaxation (4 sessions). | Behavioral: FibroQol<br>* Session 1: General information. Expectations of the patients. History of the illness. Principal and secondary symptoms in FM. Physiological mechanisms involved in the genesis of pain. Session 2: Relaxation training-I. Session 3: Diagnosis. Pharmacological and non-pharmacological treatments. Prognosis. Current model of health care in Catalonia. Units specialized in the treatment of FM. Session 4: Relaxation training-II. Session 5: Strategies to increase self-esteem and regulate emotions. Pain experience and recurrent invalidation. Social support (family and friends). Session 6: Relaxation training-III Session 7: Benefits of physical exercise in FM. Session 8: Relaxation training-IV.<br>Drug: TAU<br>* In Spain the treatment as usual provided in FMS is mainly pharmacological and adjusted to the symptomatic profile of the patient. Counselling about aerobic exercise adjusted to patients' physical limitations is usually also provided.<br>* Other names: Usual care;|
| Other: Treatment As Usual<br>Treatment As Usual. | Drug: TAU<br>* In Spain the treatment as usual provided in FMS is mainly pharmacological and adjusted to the symptomatic profile of the patient. Counselling about aerobic exercise adjusted to patients' physical limitations is usually also provided.<br>* Other names: Usual care;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness Evaluation: Revised Fibromyalgia Impact Questionnaire (FIQR) |  | Change from baseline scores at 12 months | 
| Cost-utility: Client Service Receipt Inventory (CSRI) |  | Change from baseline scores at 12 months | 
| Inflammatory markers: pro- and anti-inflammatory cytokines & hs-CRP |  | Change from baseline values at 2 months | 
| EuroQoL questionnaire (EQ-5D-5L) |  | Change from baseline scores at 12 months | 
| Structural neuroimaging: Voxel-Based Morphometry (VBM) | Analysis of morphometric changes associated with participation in the three study arms voxel-by-voxel across the brain and in functionally-defined brain regions of interest relating to meta-awareness, body awareness, memory consolidation-reconsolidation, and emotion regulation. | Change from baseline brain gray matter concentration at 2 months | 
| Functional neuroimaging: pulsed continuous arterial spin labeling (pCASL) | Analysis of changes in regional cerebral blood flow representing response to treatment throughout the brain and in a priori-specified network of brain regions postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience. | Change from baseline regional cerebral blood flow at 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Anxiety and Depression Scale (HADS) |  | Baseline, 2-month & 12-month follow-up | 
| Perceived Stress Scale (PSS-10) |  | Baseline, 2-month & 12-month follow-up | 
| Multidimensional Inventory of Subjective Cognitive Impairment (MISCI) |  | Baseline, 2-month & 12-month follow-up | 
| Pain Catastrophising Scale (PCS) |  | Baseline, 2-month & 12-month follow-up | 
| Fibromyalgia Survey Diagnostic Criteria (FSDC) |  | Baseline, 2-month & 12-month follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fibromyalgia syndrome, Mindfulness (MBSR), Neuroimaging, Cytokines, Randomized Controlled Trial, Cost-effectiveness, Psychoeducation (FibroQol)