Clinical trial NCT06669702: EXercise Therapy in Axial SpA, Inflammation and Biologic Therapy (ExTASI-B)
Official title: EXercise As an Anti-inflammatory Treatment in Axial Spondyloarthritis (axSpA) for Patients Taking Biologic Therapy: a Proof of Concept Study (ExTASI-B).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Axial Spondyloarthrithis
Inflammatory Diseases
Arthritis
Keywords: Exercise
Inflammation
Immunosenescence
Lead sponsor: Loughborough University
Sponsor class: OTHER
Collaborators: name: University Hospitals, Leicester
First posted: 2024-11-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Random allocation into either a control group or an exercise group (12-weeks of home based exercise).
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal of this randomised controlled trial study is to investigate whether exercise (brisk walking, equal to 13 on a rating of perceived exertion scale; somewhat hard) can be used as an adjuvant therapy for people living with axial spondyloarthritis and taking biologic medications to further improve their quality of life and lower their symptoms and disease burden. The main questions it aims to answer are:

Does a 12-week structured home-based aerobic exercise intervention have a favourable effect on markers of immune-mediated inflammation and symptom severity?

As a secondary aim and outcome, this study will investigate:

* The acceptability of this intervention using questionnaires with free text boxes and one-to-one semi-structured interviews in a subset (50%) of participants (Q-ExTASI-B substudy).
* The effect of the home-based intervention on circulating markers of cardiometabolic health, anthropometrical measures, and immune markers that associate with systemic inflammation.
* The effect of the home-based intervention on objective measures of physical function and exercise tolerance

The study will compare the data of a healthy group with that of people living with axial spondyloarthritis. Within the patient population, 20 of the individuals will be allocated to the exercise group (randomly), and 20 will be allocated to the usual care group. In the exercise group, participants will be asked to do 30 minutes of brisk walking five days a week for 12 weeks, and they will be visiting Loughborough University every four weeks to provide blood samples and fill out questionnaires. Participants in the usual care group will continue with their current care routine and will visit the study site to provide blood samples and questionnaire data every 4 weeks. The data from all axSpA patients will be compared to healthy controls, and subgroup analysis will be conducted to investigate the difference between the exercise group and the usual care group.

Detailed description: Over 200,000 people in the UK have axial spondyloarthritis. In 80% of cases the condition begins in the second or third decade of life. Exercise is encouraged as an essential treatment of axial spondyloarthritis (axSpA), with the potential to both promote well-being, increase flexibility and range of movement, improve posture and reduce stiffness and pain. axSpA is an inflammatory arthritis and raised levels of indicators ('markers') of this inflammatory process (e.g. CRP) can be detected in the blood of patients. These markers are released as a consequence of the condition, but some, such as TNF-alpha and interleukin-17 (IL-17), also promote further disease development. In other inflamed patient groups we have shown that regular exercise (brisk walking) can lower the levels of these pro-inflammatory markers in the blood and increase levels of anti-inflammatory markers, independently of weight loss. Despite axSpA being an inflammatory condition with prescribed medication focused on reducing inflammation there are no studies that have assessed the potential of exercise to act as an anti-inflammatory adjuvant to biologic therapy in axSpA. This research will investigate the effect of 12 weeks of a home-based walking exercise intervention on measures of systemic inflammation and body composition, well-being and measures of disease activity using established and validated methods in 20 axSpA patients on regular biologic therapy and compare this group with 20 patients on regular biologic therapy who carry on with their standard care and normal levels of activity. Also, a baseline comparison will be conducted between a group of 20 healthy individuals and axSpA patients (40).This proof-of-concept study will determine the potential of exercise as an adjuvant anti-inflammatory treatment for patients with axSpA taking biologic medication.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of axSpA by a consultant rheumatologist
* Age=/\>18 years old
* Without other significant cardiovascular comorbidities
* Receiving stable dose biologic treatment
* Able to commit to the time demands of the study

Exclusion Criteria:

* Unable to undertake exercise due to physical or psychological barriers
* Presence of hip or peripheral joint disease
* Contraindication to exercise training (American College of Sports Medicine guidelines)
* Excessively active (score of high on IPAQ)
* Unable to communicate sufficiently in English
* Female participants who are pregnant, lactating, or planning pregnancy during the course of the study.
* Inability to give informed consent or comply with testing and training protocol for any reason.
* Presence of chronic anaemia (haemoglobin less than 13.5 g/dL for men; less than 12.0 g/dL for women; or haematocrit less than 41.0% in men, less than 36.0% in women.
* Co-morbidity that the research team determine to be a contraindication to involvement

Inclusion and exclusion criteria of healthy controls:

Inclusion Criteria:

* Aged between 18 years old and 65 years old
* Not taking any long-term medication that affects inflammation or immune-mediated inflammation.
* Free from infection or infection symptoms

Exclusion criteria:

The participant may not enter the study if ANY of the following apply:

* Unable to undertake exercise due to physical or psychological barriers
* Excessively active (score of high on IPAQ)
* Unable to communicate sufficiently in English
* Female participants who are pregnant, lactating, or planning pregnancy during the course of the study.
* Inability to give informed consent or comply with testing and training protocol for any reason.
* Have been diagnosed with or are aware of at least one of the following health issues:
* Immune system disorder
* Cardiovascular and/or cardiometabolic diseases, including but not limited to high blood pressure, high triglycerides and/or cholesterol levels, diabetes mellitus, etc.
* Any chronic health condition that affects one's ability to partake in physical activity
* Musculoskeletal injury that affects one's ability to partake in physical activity

Primary outcomes:
measure: Changes in spinal pain before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks
measure: Changes in inflammatory monocyte phenotypes before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention
timeFrame: 0, 4, 8, 12, weeks.
measure: Changes in ankylosing spondylitis disease activity before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12, weeks.
measure: Changes in characteristics of T-cell cell phenotypes (senescence) before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention
timeFrame: 0, 4, 8, 12, weeks.
Secondary outcomes:
measure: Changes in tumor necrosis factor-alpha blood concentrations before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12, weeks
measure: Changes in interleukin-6 blood concentrations before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12, weeks
measure: Changes in stimulated cytokine concentration released from isolated Peripheral blood mononuclear cells (PBMCs) before (week 0 - baseline), and after (weeks 12), the 12-week home based exercise intervention.
timeFrame: 0,12, weeks
measure: Changes in the symptom burden of ankylosing spondylitis before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12, weeks.
measure: Changes in work productivity before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12, weeks.
measure: Changes in subjective physical activity before (week 0 - baseline), and after (week 12) the 12-week home based exercise intervention.
timeFrame: 0, 12, weeks.
measure: Adherence to biologic medicines before (week 0 - baseline), and during (week 4, 8, 12) the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in quality of life of the patients before (week 0 - baseline), and during (weeks 4, 8, 12) the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in the general health-related quality of life before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home-based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in overall health status before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home-based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in daytime sleepiness before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home-based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in night time sleep quality before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home-based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in gastrointestinal symptoms before (week 0 - baseline), and during (weeks 4, 8, and 12), the 12-week home-based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in physical function before (week 0 - baseline), and after (week 12) the 12-week home based exercise intervention.
timeFrame: 0, 12 weeks.
measure: Changes in secondary physical function before (week 0 - baseline), and after (week 12) the 12- week home based exercise intervention.
timeFrame: 0, 12 weeks.
measure: Changes in exercise capacity before (week 0 - baseline), and after (week 12), the 12-week home-based exercise intervention.
timeFrame: 0, 12 weeks.
measure: Changes in body mass before (week 0 - baseline), and during (weeks 4, 8, and 12) the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in height before (week 0 - baseline), and during (weeks 4, 8, and 12) the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in waist circumference before (week 0 - baseline), and during (weeks 4, 8, and 12) the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in hip circumference before (week 0 - baseline), and during (weeks 4, 8, and 12) the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Changes in body fat percentage before (week 0 - baseline), and during (weeks 4, 8, and 12) the 12-week home based exercise intervention.
timeFrame: 0, 4, 8, 12 weeks.
measure: Sedentary activity minutes per day
timeFrame: 7 days in the 2 week period prior to baseline assessment.
measure: Light physical activity minutes per day
timeFrame: 7 days in the 2 week period prior to baseline assessment.
measure: Moderate to vigorous physical activity minutes per day
timeFrame: 7 days in the 2 week period prior to baseline assessment.
Other outcomes:
Locations:
city: Loughborough
country: United Kingdom
facility: Loughborough University, National Centre for Sport and Exercise Medicine
state: Leicestershire
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS trust
Study officials:
affiliation: University Hospitals, Leicester
name: Arumugam Moorthy, Dr
role: PRINCIPAL_INVESTIGATOR
References:
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