Clinical trial NCT05781763: High-intensity Training in Patients With Spondyloarthritis: a Randomized Controlled Trial
Official title: High-intensity Exercise Based on Self-management With Digital Coaching in Patients With Spondyloarthritis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Axial Spondyloarthritis
Lead sponsor: Halmstad University
Sponsor class: OTHER
First posted: 2023-03-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 67
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned into intervention- and control groups. Simple randomization will be used for equal group allocation at three different rheumatology clinics in southern Sweden. The patients will choose a sealed note in which one of the words "intervention" or "control" is written, when the baseline assessment is completed at the first measurement occasion.
Primary purpose: TREATMENT

Brief summary: Project summary

Background: For people diagnosed with a spondyloarthritis (SpA) e.g. ankylosing spondylitis or undifferentiated spondyloarthritis, physical activity and exercise are important components in the self-management. Exercise, in addition to physical and mental symptoms related to the disease can easily feel overwhelming to exercise, and low adherence may result. By studying the effects of high-intensity interval training (HIIT) in comparison with training as usual on physiological, inflammatory, and self-reported disease parameters in patients with SpA, we intend to further investigate the short-term and longitudinal training effects, and refine the knowledge to tailor, coach, and stimulate to self-performed HIIT.

Objective: The purpose of this study is to investigate the short- and long-term effects of high- intensity interval training (HIIT) on physiological, inflammatory, and self-reported health parameters in patients with SpA. The aim is also to study the adherence to physical activity and exercise recommendations.

Design: A randomized controlled trial (RCT) design. Participants: One hundred adults with a confirmed axial SpA from rheumatology clinics in southern Sweden will be recruited and randomized into two groups, the intervention group and the control group.

Intervention: Three high-intensity training sessions per week for three months, of which two interval sessions, with coaching both from a clinical physiotherapist and digital devices (watch and app) followed by nine months with sporadic coaching. The control group will go on with exercise as usual.

Primary outcome: Self-reported disease activity, inflammatory biomarkers (acute phase proteins).

Secondary outcomes: Physical fitness (aerobic capacity (VO2max), blood pressure, grep strength), body composition and self-reported physical function, health status, well-being, pain, fatigue, adherence to physical activity and exercise recommendations, and confidence in one's own ability to manage pain, symptoms and high-intensity exercise, and additional serum biomarkers.

Detailed description: Introduction SpA is an umbrella term for a group of inflammatory diseases with a prevalence that varies between 0.2% - 1.6% globally. SpA can be divided into two forms; axial SpA characterized by inflammation in the spine and pelvic joints, and in peripheral SpA characterized by inflammation in peripheral joints, entesites and dactylites. Recommended treatment consists of a combination of pharmacological and non-pharmacological interventions. The non-pharmacological treatment includes physiotherapy with disease counselling and specific training. There is an increased risk of comorbidity such as cardiovascular disease, obesity, depression and osteoporosis in patients with axSpA. The risk of several of the comorbidities that occur is considered to be reduced through an increased degree of physical activity. The increased cardiovascular risk is considered multifactorial but is partly explained by the chronic systemic inflammation and a low level of physical activity.

The effects of high-intensity interval training (HIIT) with respect to inflammatory biomarkers are poorly studied in individuals with rheumatic diseases. Also, proteins secreted by muscle cells during physical activity, myokines, and their suggested effect to counteract the inflammatory process, need to be further studied. HIIT is believed to be able to affect both the disease outcome and the increased risk of cardiovascular morbidity, but more studies are needed to obtain sufficient evidence along with new biomarkers recently found to affect inflammation that can be implemented in a general maintenance of the individuals' systemic inflammatory status. In the general population, the greatest positive effect is seen on cardiovascular disease and its risk factors during cardio training at a higher intensity. Studies show that individuals with SpA can exercise at a higher intensity level without exacerbating disease activity and that HIIT can reduce inflammation and reduce the cardiovascular risk factors for individuals with SpA.

Despite the overwhelming evidence that exercise will help in the disease management, individuals with the disease still find it difficult to make exercise a sustainable routine in their lives. Previous studies have shown that when a coach-led intervention ends, it is common with a large drop-out rate and that compliance decreases. Changing a behavior should take place gradually and over a long period of time to have the best conditions to become permanent. A person-centered approach with the opportunity to choose activity, and be able to vary activity and training sessions have proven to be important factors that increase compliance with HIIT. Active coaching, registration of heart rate level during training and estimation of perceived effort have all been shown to be important to achieve the right training intensity. Telehealth, in which health coaching is provided via telecommunications and other virtual communication devises outside traditional health care, is considered an important part of modern care, among other things, to encourage change. However, the effects of this type of intervention are still incompletely studied.

The effects of HIIT on physical, inflammatory, and self-reported health parameters needs to be further studied. The knowledge is also scarce on how to tailor the high-intensity training as a part of the self-management for individuals with SpA, with the aim to maintain regular exercise routines and sustainable health over time.

Objectives The purpose of this study is to investigate the short- and long-term effects of self-performed high-intensity interval training (HIIT) on physiological, inflammatory, and self-reported health parameters in patients with SpA. The aim is also to study the adherence to the physical activity and exercise recommendations.

The primary hypothesis in this study is that there will be significant differences between the intervention group and the control group concerning self-reported disease activity, in some of the inflammatory biomarkers (acute phase proteins and pro-inflammatory cytokines), and in adherence to vigorous intensity performed physical activity and exercise both in the short and long term.

The secondary hypothesis is that there will be significant differences between patients in the intervention group and the control group regarding physiological health (aerobic capacity, blood pressure, grip strength, body composition), and self-reported health (physical function, health status, well-being, pain, fatigue, inactivity), and in the confidence in one's own ability to manage pain, symptoms, and high-intensity training, after both three- and twelve-months follow-ups.

Methodology The results of a three-months intervention with high-intensity training, followed by nine months with customized coaching where the intervention group will be motivated and strengthened in their own confidence to continue training regularly at high-intensity levels, will be compared to the control group for primary- and secondary outcomes. The control group continues with their regular physical activity and exercise routines as before.

The patients will be recruited from rheumatological clinics in southern Sweden, through invitation via personal contact by the physiotherapist at the clinic. Participants will be randomly assigned into intervention- and control groups after baseline assessments.The baseline tests include both patients in the experimental and control groups. Baseline tests will include physiological tests, body composition, blood tests, self-reported questionnaire including different health variables, collected during one visit. After 12 weeks of intervention, and after one year the same assessment will be made.

A clinical physiotherapist at each centre will identify eligible patients and, checking the inclusion criteria in the medical record, and screen for cardiovascular or other comorbidities contraindicated for high-intensity training. After showing interest in participating, they will receive oral and written information. An informed consent will be signed by all included patients before the data collection will start. At the initial visit the physiotherapist will start by measuring the chest thumb electrocardiography (ECG). In the event of two repeated deviating results regarding the ECG, the patients will be referred to the health centre for further investigation before any inclusion.

Intervention The patients in the intervention group will be instructed to perform two HIIT/week and one further training session at moderate or high-intensity of their own choice every week mostly on their own for 12 weeks. Structured coaching will be given with support of text messages and a heart rate (HR) feedback from a fitness watch (Polar Ignite, Polar Electro Oy, Kempele, Finland). The approach is based on a person-centered care approach with self-selected activity that engages large muscle groups, such as cycling, Nordic walking, running, swimming, rowing, cross-training. During the first 12 weeks, coach-led sessions are offered on at least three occasions, during week 1, 2 and 7 with the aim of guiding the patients to the right intensity. The intensity will be individually based on the patient's max heart rate (MHR). If necessary, additional coach-led sessions will be offered. After the 12 initial weeks, the intervention continues for another nine months with customized coaching where the patients will be motivated and strengthen in their own confidence to continue with HIIT sessions. During this time, the participants will go on and register the training sessions with the fitness watch, and they will be contacted once a month by their coach for guidance.

The intervention begins with a coach-led interval session during week 1 consisting of 4x4 min intervals with 3 minutes active rest (at 50-70% of MHR) between each interval. The first session will be performed on a stationary bicycle. The session will start with a warm-up to a heart rate of 60-70% of MHR, afterwards the load will be increased to 85% of MHR in the interval with the intention to reach 90% at some point during each interval. Perceived exertion will be assessed with the RPE scale and the goal is to reach at least RPE 17 during the intervals. The session will end with a cool down at \<60% MHR. The patient will be able to choose between different interval sessions, but the total time for the intervals in each session should be 15 minutes. In addition to the two HIIT session, the patient will be instructed to perform one further high-intensity training each week at a HR of at least 75% of MHR or at RPE 14. At least one rest day should be planned in between each session.

The continuous monitoring of HR and individual coaching will be based on data available through the fitness watch and a web-based coaching platform. The coaching physiotherapist will log in as a coach and be able to follow the training sessions digitally every week. During the first four weeks, the patients will be contacted once a week by phone. After week 4, the follow-up of each patient will be based on their own wishes, but at least once/month. Three text messages/week will be sent to the patients in the intervention group during the initial 12 weeks with a reminder to stay active.

Data analysis Data analysis will be performed using Microsoft Excel and IBM SPSS (IBM SPSS Statistics for Windows). The level of significance is set to p\<0.05. Depending on if the data is normally distributed or not, appropriate statistical method will be used. If normally distributed, the main outcomes will be analyzed with two-way ANOVA. To find a minimum difference between the groups according to self-reported disease activity, a sample size calculation of 50 patients for two subgroups, approximately 100 participants, will be needed to obtain a power of 80% at a significance level of 5%.

Ethics The study will be accomplished in the terms of the Declaration of Helsinki. The Swedish Ethical Review Authority approved the study (2019-04155, 2022-03114-02). All collected study-specific data will be managed confidential and the patients' personal data will be replaced by codes. The results from the routine blood samples will be entered into the medical record in accordance guidelines and the Patient Data Act and data will then retrieved from there. Only researchers in the project will have access to the coded data for the analysis and the results will be presented at group levels. After the analyses are finished the collected data will be stored on a security-protected server at Halmstad University, and the blood samples will be stored in a biobank at FoU Spenshult.

Eligibility criteria: Inclusion Criteria:

* Axial SpA (ICD10 diagnosis of M45, M46.0, M46.1, M46.8 and M46.9).
* Fulfilling recommendations for physical activity

Exclusion Criteria:

* Changed TNF and anti-inflammatory medication the previous three months
* Cardiovascular disease
* Comorbidities making high-intensity training inappropriate
* Performing high-intensity interval training on a regular basis

Primary outcomes:
measure: Self-reported disease activity BASDAI
timeFrame: after 3 months
measure: Self-reported disease activity BASDAI
timeFrame: after 12 months
measure: Self-reported disease activity ASDAS-CRP
timeFrame: after 3 months
measure: Self-reported disease activity ASDAS-CRP
timeFrame: after 12 months
measure: Biomarker C-reaktivt protein (CRP)
timeFrame: after 3 months
measure: Biomarker C-reaktivt protein (CRP)
timeFrame: after 12 months
measure: Biomarker Pentraxin-related protein (PTX3)
timeFrame: after 3 months
measure: Biomarker Pentraxin-related protein (PTX3)
timeFrame: after 12 months
measure: Biomarker serum amyloid A1
timeFrame: after 3 months
measure: Biomarker serum amyloid A1
timeFrame: after 12 months
Secondary outcomes:
measure: Aerobic capacity VO2max
timeFrame: after 3 months
measure: Aerobic capacity VO2max
timeFrame: after 12 months
measure: Blood pressure
timeFrame: after 3 months
measure: Blood pressure
timeFrame: after 12 months
measure: Grip strength
timeFrame: after 3 months
measure: Grip strength
timeFrame: after 12 months
measure: Body composition fat percent
timeFrame: after 3 months
measure: Body composition fat percent
timeFrame: after 12 months
measure: Body composition visceral fat area
timeFrame: after 3 months
measure: Body composition visceral fat area
timeFrame: after 12 months
measure: Body mass index (BMI)
timeFrame: after 3 months
measure: Body mass index (BMI)
timeFrame: after 12 months
measure: Self-reported physical function
timeFrame: after 3 months
measure: Self-reported physical function
timeFrame: after 12 months
measure: Self-reported Health status
timeFrame: after 3 months
measure: Self-reported Health status EuroQol-5 domain (EQ-5D)
timeFrame: after 12 months
measure: Self-reported well-being
timeFrame: after 3 months
measure: Self-reported well-being
timeFrame: after 12 months
measure: Self-reported pain
timeFrame: after 3 months
measure: Self-reported pain
timeFrame: after 12 months
measure: Self-reported pain intensity
timeFrame: after 3 months
measure: Self-reported pain intensity
timeFrame: after 12 months
measure: Self-reported Fatigue
timeFrame: after 3 months
measure: Self-reported Fatigue
timeFrame: after 12 months
measure: Objective adherence to physical activity and exercise recommendations
timeFrame: after 3 months
measure: Objective adherence to physical activity and exercise recommendations
timeFrame: after 12 months
measure: Self-reported adherence to physical activity and exercise recommendations
timeFrame: after 3 months
measure: Self-reported adherence to physical activity and exercise recommendations
timeFrame: after 12 months
measure: Self-reported confidence in one's own ability to manage pain
timeFrame: after 3 months
measure: Self-reported confidence in one's own ability to manage pain
timeFrame: after 12 months
measure: Self-reported confidence in one's own ability to manage symptoms
timeFrame: after 3 months
measure: Self-reported confidence in one's own ability to manage symptoms
timeFrame: after 12 months
measure: Self-reported confidence in one's own ability to do high-intensity exercise
timeFrame: after 3 months
measure: Self-reported confidence in one's own ability to do high-intensity exercise
timeFrame: after 12 months
measure: Proinflammatory cytokin TNF-α
timeFrame: after 3 months
measure: Proinflammatory cytokin TNF-α
timeFrame: after 12 months
measure: Proinflammatory cytokin IL-6
timeFrame: after 3 months
measure: Proinflammatory cytokin IL-6
timeFrame: after 12 months
measure: Proinflammatory cytokin IL-17a
timeFrame: after 3 months
measure: Proinflammatory cytokin IL-17a
timeFrame: after 12 months
measure: Proinflammatory cytokin IL-18
timeFrame: after 3 months
measure: Proinflammatory cytokin IL-18
timeFrame: after 12 months
measure: Proinflammatory cytokin IL-21
timeFrame: after 3 months
measure: Proinflammatory cytokin IL-21
timeFrame: after 12 months
measure: Proinflammatory cytokin IL-23
timeFrame: after 3 months
measure: Proinflammatory cytokin IL-23
timeFrame: after 12 months
measure: Chemokines CXCL10
timeFrame: after 3 months
measure: Chemokines CXCL10
timeFrame: after 12 months
measure: Inflammation-related protein Vascular endothelial growth factor (VEGF-A)
timeFrame: after 3 months
measure: Inflammation-related protein Vascular endothelial growth factor (VEGF-A)
timeFrame: after 12 months
measure: Inflammation-related protein interleukin 1 receptor antagonist (IL-1Ra)
timeFrame: after 3 months
measure: Inflammation-related protein interleukin 1 receptor antagonist (IL-1Ra)
timeFrame: after 12 months
measure: Inflammation-related protein Interleukin 8 (IL-8)
timeFrame: after 3 months
measure: Inflammation-related protein Interleukin 8 (IL-8)
timeFrame: after 12 months
measure: Inflammation-related protein Macrophage Inflammatory Proteins (MIP-1a)
timeFrame: after 3 months
measure: Inflammation-related protein Macrophage Inflammatory Proteins (MIP-1a)
timeFrame: after 12 months
measure: Inflammation-related protein macrophage inflammatory protein-1β (MIP-1β)
timeFrame: after 3 months
measure: Inflammation-related protein macrophage inflammatory protein-1β (MIP-1β)
timeFrame: after 12 months
measure: Protein serum calprotectin
timeFrame: after 3 months
measure: Protein serum calprotectin
timeFrame: after 12 months
measure: CRP/albumin ratio
timeFrame: after 3 months
measure: CRP/albumin ratio
timeFrame: after 12 months
measure: Myokine irisin
timeFrame: after 3 months
measure: Myokine irisin
timeFrame: after 12 months
measure: Myokine Brain-derived neurotrophic factor (BDNF)
timeFrame: after 3 months
measure: Myokine Brain-derived neurotrophic factor (BDNF)
timeFrame: after 12 months
measure: Bone and cartilage protein Dickkopf-related protein 1 (DKK-1)
timeFrame: after 3 months
measure: Bone and cartilage protein Dickkopf-related protein 1 (DKK-1)
timeFrame: after 12 months
measure: Bone and cartilage protein osteocalcin
timeFrame: after 3 months
measure: Bone and cartilage protein osteocalcin
timeFrame: after 12 months
measure: Bone and cartilage protein sclerostin
timeFrame: after 3 months
measure: Bone and cartilage protein sclerostin
timeFrame: after 12 months
measure: Bone and cartilage protein osteopontin
timeFrame: after 3 months
measure: Bone and cartilage protein osteopontin
timeFrame: after 12 months
measure: Bone and cartilage protein fibroblast growth factor 23 (FGF-23)
timeFrame: after 3 months
measure: Bone and cartilage protein fibroblast growth factor 23 (FGF-23)
timeFrame: after 12 months
measure: Bone and cartilage protein Bone morphogenetic protein 7 (BMP- 7)
timeFrame: after 3 months
measure: Bone and cartilage protein Bone morphogenetic protein 7 (BMP- 7)
timeFrame: after 12 months
measure: Bone and cartilage protein matrix metalloproteinase-3 (MMP-3)
timeFrame: after 3 months
measure: Bone and cartilage protein matrix metalloproteinase-3 (MMP-3)
timeFrame: after 12 months
measure: Liver-derived protein Fibroblast growth factor 21 (FGF-21)
timeFrame: after 3 months
measure: Liver-derived protein Fibroblast growth factor 21 (FGF-21)
timeFrame: after 12 months
measure: Apolipoprotein B (ApoB)
timeFrame: after 3 months
measure: Apolipoprotein B (ApoB)
timeFrame: after 12 months
measure: Apolipoprotein A1 (ApoA1)
timeFrame: after 3 months
measure: Apolipoprotein A1 (ApoA1)
timeFrame: after 12 months
Other outcomes:
Locations:
city: Halmstad
country: Sweden
facility: Halmstad University
state: Halland
Study officials:
affiliation: Dept. of Environmental and Biosciences, Halmstad University, Sweden
name: Haglund, Assoc. prof.
role: PRINCIPAL_INVESTIGATOR
References: