Cost-utility and Immuno-inflammatory Effects of the FIBROWALK in Patients With Fibromyalgia (the On&Out Study)

Study Overview
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Brief Summary
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The present project will evaluate through a randomised controlled clinical trial with 6-month follow-up, the efficacy and cost-utility (6-month time horizon) of the multicomponent FIBROWALK programme in an online (i.e., FIBRO-On) and outdoor (i.e., FIBRO-Out) adjunctive to usual care (HC) format, as compared to HC. In order to determine the mechanisms of action of the clinical effects of the interventions studied 6 months after the start of treatment, pre-post changes will be evaluated in various psychological variables considered to be mediators from a theoretical point of view, as well as in immuno-inflammatory markers with evidence of alteration in FM and/or potentially modifiable by the interventions proposed (i.e. IL-6, CXCL8, IL-17A, IL-4, IL-10, high-sensitivity C-reactive protein). In the field of personalised treatment in chronic pain, the design of the present study with 3 treatment branches will also make it possible to establish whether certain patient profiles or baseline psychobiological characteristics can predict the short- and medium-term clinical response to the treatments studied.

Detailed Description
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Introduction: The On&Out study is aimed at assessing the efficacy, cost-utility and immuno-inflammatory underpinnings of the FIBROWALK multicomponent intervention conducted in two different settings: online (FIBRO-On) or outdoors (FIBRO-Out). Both interventions have proved to be efficacious in the short-term but there is no study assessing their comparative efficacy nor their long-term effects. This study will also evaluate the cost-utility (6-month time-horizon) and the effects in blood biomarkers level of both interventions for the first time. The objectives of this 6-month, randomized, controlled trial (RCT) are (i) to examine the efficacy and cost-utility of adding FIBRO-On or FIBRO-Out to treatment-as-usual (TAU) for individuals with fibromyalgia; (ii) to identify pre-post differences in levels in blood biomarkers in the three study arms and (iii) to analyze the role of some psychological process variables as mediators of 6-month clinical outcomes. Methods and analysis: Participants will be 225 individuals with fibromyalgia recruited at Vall d'Hebron Institute of Research (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs TAU+FIBRO-On vs TAU+FIBRO-Out. A comprehensive assessment to collect functional impact, pain, fatigue, depressive-anxiety symptoms, physical function, kinesiophobia, pain catastrophism, quality of life, costs, and psychological process variables will be conducted pre-intervention, at half of the intervention (6 weeks, post-intervention (12 weeks), and at 6-month follow-up. Changes in immuno-inflammatory biomarkers (i.e. IL-6, CXCL8, IL-17A, IL-4, IL-10, and high-sensitivity C reactive protein) and Brain-Derived Neurotrophic Factor will be evaluated in 50% of the sample at pre- and post-treatment. Linear mixed-effects models using restricted maximum likelihood, mediational models and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed.

Official Title
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Cost-utility and Immuno-inflammatory Underpinnings of the FIBROWALK Multicomponent Therapy in Online or Outdoor Format in Fibromyalgia: a Randomised, Controlled Trial (the On&Out Study)

Conditions
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Fibromyalgia

Intervention / Treatment
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* Behavioral: TAU + FIBRO-On
* Behavioral: TAU + FIBRO-Out
* Other: Treatment as Usual (TAU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both sexes, between 18 and 65 years of age. Diagnosis of fibromyalgia according to the ACR 2010/2011 criteria. Understanding Spanish. Exclusion Criteria: Psychological treatment (within the last year) or current. Comorbid presence of severe mental disorder (e.g. schizophrenia) or other terminal clinical conditions or scheduled treatments that may interrupt study follow-up. Inability to complete the weekly sessions/modules of the programme on a regular basis. Being in litigation with the health system with the aim of obtaining a permanent leave of absence.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAU + FIBRO-On<br>FIBRO-On is a virtual multicomponent non-pharmacological program based on Pain Neuroscience Education (PNE), therapeutic exercise, Cognitive Behavioural Therapy (CBT) and Mindfulness Training | Behavioral: TAU + FIBRO-On<br>* Group treatment protocol of 12 weekly 60 minute sessions (virtual intervention)<br>|
| Active Comparator: TAU + FIBRO-Out<br>FIBRO-Out is a outdoor multicomponent non-pharmacological program based on Pain Neuroscience Education (PNE), therapeutic exercise, Cognitive Behavioural Therapy (CBT) and Mindfulness Training | Behavioral: TAU + FIBRO-Out<br>* Group treatment protocol of 12 weekly 120 minute sessions (outdoor intervention)<br>|
| Active Comparator: Treatment as Usual (TAU)<br>Treatment-as-Usual (TAU) consisted of the prescribed drugs adapted to the symptomatic profile of each patient and basic face to face and written advice on PNE and aerobic exercise adapted to the physical capacities of the patients at the beginning of the study.patient | Other: Treatment as Usual (TAU)<br>* Standard pharmacological treatment usually provided to patients with fibromyalgia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Revised Fibromyalgia Impact Questionnaire (FIQR) | The FIQR comprises three dimensions: physical dysfunction (scores from 0 to 30), overall impact (scores from 0 to 20), and intensity of the symptoms (scores from 0 to 50) is used to measure the impact generated by FM during the last week. It consists of 21 items, which are answered on a numerical rating scale of 11 points (from 0 to 10). Total scores can range from 0 to 100, with higher scores reflecting greater deterioration. | Change from baseline values at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual-analogue scale of perceived pain (VAS-Pain) | Patients indicate their pain during the last week on a 10 cm line. Total scores range from 0 to 10, where higher scores indicate a greater pain. | Change from baseline values at 6 months | 
| Visual-analogue scale of perceived fatigue(VAS-Fatigue) | Patients indicate their fatigue during the last week on a 10 cm line. Patients indicate their pain during the last week on a 10 cm line. Total scores range from 0 to 10, where higher scores indicate a greater fatigue. | Change from baseline values at 6 months | 
| Hospital Anxiety and Depression Scale (HADS) | HADS is used to quantify the severity of anxiety and depression symptoms. It consists of two dimensions (anxiety and depression) of 7 items each responding on a Likert scale of 4 points. Total scores of each scale (HADS-A and HADSD) range from 0 to 21, where higher scores indicate greater severity of symptoms. | Change from baseline values at 6 months | 
| Perceived Stress Scale (PSS) | PSS is used to evaluate the stress perceived by people during the last month. This study will use a 4 item version. The response format of this scale is 5-point Likert type. Total scores range from 0 to 16, with higher scores indicating greater perceived stress | Change from baseline values at 6 months | 
| Short Form-36 Health Survey (SF-36) | Physical Function of the 36-Item Short Form Survey (SF-36) was used to measure physical function.This dimension comprises a total of 10 items, which are answered on a Likert scale of 3 points. Total scores on each scale are then transformed and can range from 0 to 100, with higher scores indicate better physical function. | Change from baseline values at 6 months | 
| EuroQoL-5D (EQ-5D) | An instrument for assessing health-related quality of life. It consists of two parts: the first part assesses the individual's difficulties in relation to mobility, self-care, pain/discomfort and anxiety/depression; and the second part assesses the patient's current perceived health status on an analogue-visual scale from 0 to 100. | Change from baseline values at 6 months | 
| Client Service Receipt Inventory (CSRI) | Questionnaire for economic evaluation. The version used in this study is designed to retrospectively collect data on the use of health and social services during the previous 6 months. | Change from baseline values at 6 months | 
| Pain Catastrophising Scale (PCS) | PCS is used to evaluate catastrophic thoughts associated with pain. It consists of three dimensions (rumination, magnification, and helplessness) of 13 items in total, which are answered on a Likert scale of 5 points. Total scores on each scale range from 0 to 52, with higher scores indicating more catastrophic thoughts. | Change from baseline values at 6 months | 
| Psychological inflexibility in pain scale (PIPS) | A 12-item scale that assesses psychological inflexibility in pain patients and includes two factors: avoidance and cognitive fusion with pain. Respondents are asked to rate items on a 7-point scale that ranges from 1 (never true) to 7 (always true). Higher scores indicate greater levels of psychological inflexibility. | Change from baseline values at 6 months | 
| Tampa Scale for kinesiophobia (TSK-11) | TSK-11 is used to assess fear of pain and movement. It consists of 11 items, which are answered on a Likert scale of 4 points. Total scores of each scale range from 11 to 44, where higher scores indicate a greater fear of pain and movement. | Change from baseline values at 6 months | 
| The Patient Global Impression of Change (PGIC) | Is a measure that has been frequently used as indicators of meaningful overall change [on a 7-point Likert scale, from 1 = Much better to 7 = Much worse] in treatments for chronic pain. | Change from baseline values at 6 months | 
| Pain Specific Impression of Change (PSIC) | The PSIC asks about the impression of change in more specific domains than PGIC: physical and social functioning, work-related activities, mood, and pain [on a 7-point Likert scale, from 1 = Much better to 7 = Much worse]. | Change from baseline values at 6 months | 
| Adverse effects of treatments | Ad hoc measure to check for the presence of negative effects of psychological treatments. | Change from baseline values at 6 months | 
| Socio-demographic questionnaire | Gender, date of birth, marital status, living arrangements, educational level and employment status. | Change from baseline values at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibromyalgia, Cost-utility, multicomponent treatment, randomized controlled trial, Biomarkers