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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Fibromyalgia
• Intervention / Treatment: Behavioral: TAU + FIBRO-On; Behavioral: TAU + FIBRO-Out; Other: Treatment as Usual (TAU)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 225
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mayte Serrat, PhD; Phone Number: 6644 +34934893891; Email: mserrat@vhebron.net

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients of both sexes, between 18 and 65 years of age.
2. Diagnosis of fibromyalgia according to the ACR 2010/2011 criteria.
3. Understanding Spanish.

Exclusion Criteria:

1. Psychological treatment (within the last year) or current.
2. Comorbid presence of severe mental disorder (e.g. schizophrenia) or other terminal clinical conditions or scheduled treatments that may interrupt study follow-up.
3. Inability to complete the weekly sessions/modules of the programme on a regular basis.
4. Being in litigation with the health system with the aim of obtaining a permanent leave of absence.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment as Usual (TAU); 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); Standard pharmacological treatment usually provided to patients with fibromyalgia.
Experimental: TAU + FIBRO-On; 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; Group treatment protocol of 12 weekly 60 minute sessions (virtual intervention)
Active Comparator: TAU + FIBRO-Out; 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; Group treatment protocol of 12 weekly 120 minute sessions (outdoor intervention)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: Universitat Autonoma de Barcelona; Ministerio de Ciencia e Innovación, Spain
• Investigators: Principal Investigator: Albert Feliu, PhD, Universitat Autonoma de Barcelona

Study record dates

Study Major Dates

• Study Start (Anticipated): September 15, 2022
• Primary Completion (Anticipated): July 20, 2023
• Study Completion (Anticipated): November 20, 2023

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 15, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: randomized controlled trial; fibromyalgia; Biomarkers; multicomponent treatment; Cost-utility
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: ON&OUT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No