Clinical trial NCT04922840: Improved Cardiovascular Health for Patients With Inflammatory Joint Diseases
Official title: Improved Cardiovascular Health for Patients With Inflammatory Joint Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spondyloarthritis
Rheumatoid Arthritis
Psoriatic Arthritis
Keywords: Exercise
Cardiovascular disease
Cardiovascular risk
High-intensity training
Physiotherapy
High-intensity exercise
Inflammatory joint disease
Lead sponsor: Diakonhjemmet Hospital
Sponsor class: OTHER
Collaborators: name: The Dam Foundation
name: The Norwegian Rheumatism Association
name: Norwegian Health Association
First posted: 2021-06-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be allocated 1:1 according to a computer-generated randomization scheme, stratified by sex
Primary purpose: TREATMENT

Brief summary: Inflammatory joint diseases (IJD) are autoimmune diseases with common symptoms of joint inflammation, pain, stiffness and fatigue. Compared to the general population, this large patient-group has an increased risk of cardiovascular disease (CVD) and CVD-related mortality. Patients with IJD call for improved CVD screening and risk management as well as access to evidence-based non-pharmacological treatment alternatives. Evidence supports high intensity training (HIIT) in mitigating risk of CVD and inflammation, but the evidence of these cardioprotective benefits is unclear in patients with IJD and the feasibility of HIIT protocols in daily clinical care needs to be addressed. Cardiorespiratory fitness (CRF) is an important physiological marker and highly correlated to risk of CVD. Despite strong recommendations, routine assessment of CRF is seldom performed in clinical care.

The ExeHeart study will assess the potential cardioprotective and disease-modifying effect of HIIT in IJD in a randomized controlled trial. Furthermore, the ExeHeart-study will report on the validity of non-exercise measures of cardiorespiratory fitness (eCRF) measures for use in daily clinical care. Additionally, we will explore the feasibility of HIIT by addressing adherence and fidelity to the HIIT treatment protocol in a primary care setting

Detailed description: The study is a two-armed randomized controlled trial (RCT). Patients aged 18-70 years presenting with inflammatory joint disease at the Preventive Cardio-Rheuma clinic at Diakonhjemmet hospital (Oslo) will be included if eligible for the study. Succeeding baseline testing, participants are randomized to either experimental group (high-intensity exercise-HIIT) or control group (usual care).

The research questions are:

1. Is a 12-week HIIT program effective on VO2peak, inflammatory markers and risk of cardiovascular disease in patients with inflammatory joint disease and what is the association between VO2peak and disease-specific and cardiovascular disease-related variables?
2. Is a non-exercise cardio-respiratory fitness algorithm (eCRF) valid in determining longitudinal change in VO2peak in patients with inflammatory joint disease?
3. How feasible is a HIIT intervention in primary care in patients with inflammatory joint disease in terms of adherence and fidelity to the exercise program?

The primary analysis will be a between group comparison of VO2peak levels. This will be carried out according to the intention-to-treat principle, and done by the analysis of covariance (ANCOVA), adjusting for VO2peak values at baseline along with stratification factors used in the randomization. Secondary analyses will include between group comparisons on secondary endpoints, as well as comparisons in the per protocol population. No adjustment for multiple testing will be done.

The association between VO2peak and changes in inflammatory markers, disease activity and CVD risk will be assessed using multiple regression.

The validity of eCRF models to accurately detect longitudinal change in VO2peak from baseline to 3-month and 6-month follow-up will be assessed with Pearson or Spearman correlation by comparing VO2peak derived from a cardiopulmonary exercise test to eCRF.

The feasibility of a HIIT program and adherence will be examined with descriptive statistics. Adherence to the prescribed HIIT intervention will be recorded by attendance to exercise sessions. Quality of treatment delivery will be quantified as the number of exercise sessions complying with the planned exercise intensity and number of exercise sessions requiring dose modifications such as lower exercise intensity or early session termination. At the 3-month timepoint, an electronic questionnaire will be distributed to patients in the HIIT group. Questions regarding feasibility and implementation fidelity will address patients' acceptability and satisfaction with the HIIT program. The ExeHeart study will also include semi-structured interviews, targeting physiotherapists in charge of supervising the exercise sessions and 5-7 patients in the intervention group. The interviews will explore barriers and facilitators in exercise adherence, experience with the protocol and perceived effects of exercise.

Eligibility criteria: Inclusion Criteria:

* Age: 18-70
* BMI: 18.5-40
* Inflammatory joint disease verified by physician
* Able to walk unaided and continuously for ≥ 15 min.
* Norwegian or English speaking

Exclusion Criteria:

* Sustained lower extremity injury ≤12 months, including surgery
* Neurological disease
* Absolute contraindication to maximal exercise test
* Cognitive impairment
* Participation in structured high-intensity exercise ≥ 1/week in the last 3 months

Primary outcomes:
measure: Peak oxygen uptake - VO2peak ml/kg/min
timeFrame: 3 months post baseline
Secondary outcomes:
measure: Peak oxygen uptake - VO2peak L/min
timeFrame: 3 months post baseline
measure: Peak oxygen uptake - VO2peak ml/kg/min
timeFrame: Baseline
measure: Peak oxygen uptake - VO2peak ml/kg/min
timeFrame: 6 months post baseline
measure: Peak oxygen uptake - VO2peak L/min
timeFrame: Baseline
measure: Peak oxygen uptake - VO2peak L/min
timeFrame: 6 months post baseline
measure: Change in VO2peak (ml/kg/min) from baseline to 3 months past baseline
timeFrame: 3 months post baseline
measure: Change in VO2peak (ml/kg/min) from baseline to 6 months post baseline
timeFrame: 6 months
measure: Change in VO2peak L/min from baseline to 3 months post baseline
timeFrame: 3 months post baseline
measure: Change in VO2peak L/min from baseline to 6 months post baseline
timeFrame: 6 months post baseline
measure: Body composition
timeFrame: Baseline
measure: Body composition
timeFrame: 3 months post baseline
measure: Body composition
timeFrame: 6 months post baseline
measure: Ventilatory threshold 1
timeFrame: Baseline
measure: Ventilatory threshold 1
timeFrame: 3 months post baseline
measure: Ventilatory threshold 1
timeFrame: 6 months post baseline
measure: Ventilatory threshold 2
timeFrame: Baseline
measure: Ventilatory threshold 2
timeFrame: 3 months post baseline
measure: Ventilatory threshold 2
timeFrame: 6 months post baseline
measure: Breathing reserve
timeFrame: Baseline
measure: Breathing reserve
timeFrame: 3 months post baseline
measure: Breathing reserve
timeFrame: 6 months post baseline
measure: Oxygen pulse
timeFrame: Baseline
measure: Oxygen pulse
timeFrame: 3 months post baseline
measure: Oxygen pulse
timeFrame: 6 months post baseline
measure: Ventilatory equivalents for oxygen (VE/VO2)
timeFrame: Baseline
measure: Ventilatory equivalents for oxygen (VE/VO2)
timeFrame: 3 months post baseline
measure: Ventilatory equivalents for oxygen (VE/VO2)
timeFrame: 6 months post baseline
measure: Ventilatory equivalents for carbon dioxide(VE/VCO2)
timeFrame: Baseline
measure: Ventilatory equivalents for carbon dioxide(VE/VCO2)
timeFrame: 3 months post baseline
measure: Ventilatory equivalents for carbon dioxide (VE/VCO2)
timeFrame: 6 months post baseline
measure: Respiratory Exchange Ratio (RER)
timeFrame: Baseline
measure: Respiratory Exchange Ratio (RER)
timeFrame: 3 months post baseline
measure: Respiratory Exchange Ratio (RER)
timeFrame: 6 months post baseline
measure: Blood lactate concentration
timeFrame: Baseline
measure: Blood lactate concentration
timeFrame: 3 months post baseline
measure: Blood lactate concentration
timeFrame: 6 months post baseline
measure: C-Reactive protein
timeFrame: Baseline
measure: C-Reactive protein
timeFrame: 3 months post baseline
measure: C-Reactive protein
timeFrame: 6 months post baseline
measure: Erythrocyte Sedimentation Rate
timeFrame: Baseline
measure: Erythrocyte Sedimentation Rate
timeFrame: 3 months post baseline
measure: Erythrocyte Sedimentation Rate
timeFrame: 6 months post baseline
measure: Total cholesterol
timeFrame: Baseline
measure: Total cholesterol
timeFrame: 3 months post baseline
measure: Total cholesterol
timeFrame: 6 months post baseline
measure: High-density lipoproteins
timeFrame: Baseline
measure: High-density lipoproteins
timeFrame: 3 months post baseline
measure: High-density lipoproteins
timeFrame: 6 months post baseline
measure: Low-density lipoproteins
timeFrame: Baseline
measure: Low-density lipoproteins
timeFrame: 3 months post baseline
measure: Low-density lipoproteins
timeFrame: 6 months post baseline
measure: Triglycerides
timeFrame: Baseline
measure: Triglycerides
timeFrame: 3 months post baseline
measure: Triglycerides
timeFrame: 6 months post baseline
measure: Blood pressure
timeFrame: Baseline
measure: Blood pressure
timeFrame: 3 months post baseline
measure: Blood pressure
timeFrame: 6 months post baseline
measure: Body Mass Index
timeFrame: Baseline
measure: Body Mass Index
timeFrame: 3 months post baseline
measure: Body Mass Index
timeFrame: 6 months post baseline
measure: Waist circumference
timeFrame: Baseline
measure: Waist circumference
timeFrame: 3 months post baseline
measure: Waist circumference
timeFrame: 6 months post baseline
measure: Resting heart rate
timeFrame: Baseline
measure: Resting heart rate
timeFrame: 3 months post baseline
measure: Resting heart rate
timeFrame: 6 months post baseline
measure: Health-related quality of life, EuroQoL (EQ5D-5L)
timeFrame: Baseline
measure: Health-related quality of life, EuroQoL (EQ5D-5L)
timeFrame: 3 months post baseline
measure: Health-related quality of life, EuroQoL (EQ5D-5L)
timeFrame: 6 months post baseline
measure: Frequency of medication
timeFrame: Baseline
measure: Dosage of medication
timeFrame: Baseline
measure: Dosage of medication
timeFrame: 3 months post baseline
measure: Frequency of medication
timeFrame: 3 months post baseline
measure: Dosage of medication
timeFrame: 6 months post baseline
measure: Frequency of medication
timeFrame: 6 months post baseline
measure: Self-reported fatigue
timeFrame: Baseline
measure: Self-reported fatigue
timeFrame: 3 months post baseline
measure: Self-reported fatigue
timeFrame: 6 months post baseline
measure: Self-reported pain
timeFrame: Baseline
measure: Self-reported pain
timeFrame: 3 months post baseline
measure: Self-reported pain
timeFrame: 6 months post baseline
measure: Self-reported physical activity (HUNT)
timeFrame: Baseline
measure: Self-reported physical activity (HUNT)
timeFrame: 3 months post baseline
measure: Self-reported physical activity (HUNT)
timeFrame: 6 months post baseline
measure: SCORE2
timeFrame: Baseline
measure: SCORE2
timeFrame: 3 months post baseline
measure: SCORE2
timeFrame: 6 months post baseline
measure: Forced vital capacity
timeFrame: Baseline
measure: Forced vital capacity
timeFrame: 3 months post baseline
measure: Forced vital capacity
timeFrame: 6 months post baseline
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: Baseline
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: 3 months post baseline
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: 6 months post baseline
measure: FEV1/FVC ratio
timeFrame: Baseline
measure: FEV1/FVC ratio
timeFrame: 3 months post baseline
measure: FEV1/FVC ratio
timeFrame: 6 months post baseline
measure: Forced expiratory flow
timeFrame: Baseline
measure: Forced expiratory flow
timeFrame: 3 months post baseline
measure: Forced expiratory flow
timeFrame: 6 months post baseline
measure: Peak expiratory flow (PEF)
timeFrame: Baseline
measure: Peak expiratory flow (PEF)
timeFrame: 3 months post baseline
measure: Peak expiratory flow (PEF)
timeFrame: 6 months post baseline
measure: Maximum voluntary ventilation (MVV)
timeFrame: Baseline
measure: Maximum voluntary ventilation (MVV)
timeFrame: 3 months post baseline
measure: Maximum voluntary ventilation (MVV)
timeFrame: 6 months post baseline
measure: Psoriatic Arthritis Impact of Disease (PsAID)
timeFrame: Baseline
measure: Psoriatic Arthritis Impact of Disease (PsAID)
timeFrame: 3 months post baseline
measure: Psoriatic Arthritis Impact of Disease (PsAID)
timeFrame: 6 months post baseline
measure: Rheumatoid arthritis impact of disease (RAID)
timeFrame: Baseline
measure: Rheumatoid arthritis impact of disease (RAID)
timeFrame: 3 months post baseline
measure: Rheumatoid arthritis impact of disease (RAID)
timeFrame: 6 months post baseline
measure: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: Baseline
measure: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: 3 months post baseline
measure: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: 6 months post baseline
measure: Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: Baseline
measure: Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: 3 months post baseline
measure: Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: 6 months post baseline
measure: Bath Ankylosing Spondylitis Global Score (BAS-G)
timeFrame: Baseline
measure: Bath Ankylosing Spondylitis Global Score (BAS-G)
timeFrame: 3 months post baseline
measure: Bath Ankylosing Spondylitis Global Score (BAS-G)
timeFrame: 6 months post baseline
measure: Ankylosing Spondylitis Disease Activity Score (ASDAS)
timeFrame: 3 months post baseline
measure: Ankylosing Spondylitis Disease Activity Score (ASDAS)
timeFrame: 6 months post baseline
measure: Ankylosing Spondylitis Disease Activity Score (ASDAS)
timeFrame: Baseline
measure: Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28)
timeFrame: Baseline
measure: Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28)
timeFrame: 3 months post baseline
measure: Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28)
timeFrame: 6 months post baseline
measure: Disease Activity in PSoriatic Arthritis (DAPSA)
timeFrame: Baseline
measure: Disease Activity in PSoriatic Arthritis (DAPSA)
timeFrame: 3 months post baseline
measure: Disease Activity in PSoriatic Arthritis (DAPSA)
timeFrame: 6 months post baseline
measure: Post-exercise questionnaire
timeFrame: 3 months post baseline
measure: Use of healthcare services
timeFrame: Baseline
measure: Use of healthcare services
timeFrame: 3 months post baseline
measure: Use of healthcare services
timeFrame: 6 months post baseline
measure: Smoking status
timeFrame: Baseline
measure: Smoking status
timeFrame: 3 months post baseline
measure: Smoking status
timeFrame: 6 months post baseline
measure: Snuff status
timeFrame: Baseline
measure: Snuff status
timeFrame: 3 months post baseline
measure: Snuff status
timeFrame: 6 months post baseline
measure: Peak heart rate
timeFrame: Baseline
measure: Peak heart rate
timeFrame: 3 months post baseline
measure: Peak heart rate
timeFrame: 6 months post baseline
measure: Augmentation index
timeFrame: Baseline
measure: Augmentation index
timeFrame: 3 months post baseline
measure: Augmentation index
timeFrame: 6 months post baseline
measure: Pulse Wave Velocity
timeFrame: Baseline
measure: Pulse Wave Velocity
timeFrame: 3 months post baseline
measure: Pulse Wave Velocity
timeFrame: 6 months post baseline
measure: Exercise self-efficacy
timeFrame: Baseline
measure: Exercise self-efficacy
timeFrame: 3 months post baseline
measure: Exercise self-efficacy
timeFrame: 6 months post baseline
measure: Exercise frequency
timeFrame: 3 months post baseline
measure: Exercise intensity
timeFrame: 3 months post baseline
measure: Exercise duration
timeFrame: 3 months post baseline
measure: Early session termination
timeFrame: 3 months post baseline
measure: Exercise-related adverse events
timeFrame: 3 months post baseline
measure: Self-reported cardiovascular health and symptoms
timeFrame: Baseline
measure: Self-reported cardiovascular health and symptoms
timeFrame: 3 months post baseline
measure: Self-reported cardiovascular health and symptoms
timeFrame: 6 months post baseline
measure: Self-report change in physical fitness
timeFrame: 3 months post baseline
measure: Self-report change in physical fitness
timeFrame: 6 months post baseline
measure: Self-report exercise habits
timeFrame: 3 months post baseline
measure: Self-report exercise habits
timeFrame: 6 months post baseline
measure: Corona virus 19 infection
timeFrame: 3 months post baseline
measure: Corona virus 19 infection
timeFrame: 6 months post baseline
measure: Corona virus 19 quarantine
timeFrame: 3 months post baseline
measure: Corona virus 19 quarantine
timeFrame: 6 months post baseline
measure: Maximum minute ventilation at peak exercise (VEmax, L/min)
timeFrame: Baseline
measure: Maximum minute ventilation at peak exercise (VEmax, L/min)
timeFrame: 3 months post baseline
measure: Maximum minute ventilation at peak exercise (VEmax, L/min)
timeFrame: 6 months post baseline
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Diakonhjemmet Hospital
Study officials:
affiliation: National Resource Center for Rehabilitation in Rheumatology
name: Anne Therese Tveter, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Norden KR, Dagfinrud H, Semb AG, Hisdal J, Viktil KK, Sexton J, Fongen C, Skandsen J, Blanck T, Metsios GS, Tveter AT. Effect of high-intensity exercise on cardiorespiratory fitness, cardiovascular disease risk and disease activity in patients with inflammatory joint disease: protocol for the ExeHeart randomised controlled trial. BMJ Open. 2022 Feb 17;12(2):e058634. doi: 10.1136/bmjopen-2021-058634.