Psoriatic Arthritis, Rheumatoid Arthritis, Spondyloarthritis
Conditions
Keywords
Exercise, Cardiovascular disease, Cardiovascular risk, High-intensity training, Physiotherapy, High-intensity exercise, Inflammatory joint disease
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.
Interventions
BEHAVIORALHigh-intensity exercise (HIIT)
12 week intervention: Two weekly sessions of 35-40 min exercise: 10 min warm-up, followed by 4x4 min at 90-95% peak heart rate (HRpeak) interspaced by 2-3 min active breaks at 60-70% HRpeak and a third weekly session with continuous exercise for a minimum of 40 min at moderate intensity.
Sponsors
The Dam Foundation
The Norwegian Rheumatism Association
Norwegian Health Association
Diakonhjemmet Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
The trial is single-blinded with investigator (KRN) masked for group allocation to reduce risk of bias. Patients are not blinded to treatment exposure nor study hypothesis.
Intervention model description
Participants will be allocated 1:1 according to a computer-generated randomization scheme, stratified by sex
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak oxygen uptake - VO2peak ml/kg/min | 3 months post baseline | VO2peak, expressed in milliliters of oxygen per kilogram of body weight per minute (ml/kg/min). VO2peak will be measured by a Cardiopulmonary Exercise test (CPET) on a treadmill, using electrocardiogram (ECG), breath-by-breath gas analyzing system, blood pressure (BP) monitor, pulse oximetry, and Borg rating of perceived exertion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak oxygen uptake - VO2peak L/min | 3 months post baseline | VO2peak, expressed in liters per minute. VO2peak will be measured by a Cardiopulmonary Exercise test (CPET) on a treadmill, using electrocardiogram (ECG), breath-by-breath gas analyzing system, blood pressure (BP) monitor, pulse oximetry, and Borg rating of perceived exertion |
| Maximum voluntary ventilation (MVV) | Baseline | Measure of the maximum amount of air that can be inhaled and exhaled in one minute. Measured over a 6- or 12-second time period, extrapolated to a value for one minute, expressed in liters/minute (L/min)- obtained from spirometry |
| Peak oxygen uptake - VO2peak ml/kg/min | Baseline | VO2peak, expressed in milliliters of oxygen per kilogram of body weight per minute (ml/kg/min). VO2peak will be measured by a Cardiopulmonary Exercise test (CPET) on a treadmill, using electrocardiogram (ECG), breath-by-breath gas analyzing system, blood pressure (BP) monitor, pulse oximetry, and Borg rating of perceived exertion (RPE 0-10) |
| Change in VO2peak (ml/kg/min) from baseline to 3 months past baseline | 3 months post baseline | Change in VO2peak, expressed in milliliters of oxygen per kilogram of body weight per minute from baseline to 6 months (3 months post intervention) . VO2peak will be measured by a Cardiopulmonary Exercise test (CPET) on a treadmill, using electrocardiogram (ECG), breath-by-breath gas analyzing system, blood pressure (BP) monitor, pulse oximetry, and Borg rating of perceived exertion |
| Change in VO2peak (ml/kg/min) from baseline to 6 months post baseline | 6 months | Change in VO2peak, expressed in milliliters of oxygen per kilogram of body weight per minute from baseline to 6 months (3 months post intervention) . VO2peak will be measured by a Cardiopulmonary Exercise test (CPET) on a treadmill, using electrocardiogram (ECG), breath-by-breath gas analyzing system, blood pressure (BP) monitor, pulse oximetry, and Borg rating of perceived exertion |
| Change in VO2peak L/min from baseline to 3 months post baseline | 3 months post baseline | VO2peak, expressed in liters per minute(L/min). VO2peak will be measured by a Cardiopulmonary Exercise test (CPET) on a treadmill, using electrocardiogram (ECG), breath-by-breath gas analyzing system, blood pressure (BP) monitor, pulse oximetry, and Borg rating of perceived exertion |
| Change in VO2peak L/min from baseline to 6 months post baseline | 6 months post baseline | VO2peak, expressed in liters per minute(L/min). VO2peak will be measured by a Cardiopulmonary Exercise test (CPET) on a treadmill, using electrocardiogram (ECG), breath-by-breath gas analyzing system, blood pressure (BP) monitor, pulse oximetry, and Borg rating of perceived exertion |
| Body composition | Baseline | Body scan to estimate total and regional distribution of lean body mass and fat mass |
| Ventilatory threshold 1 | Baseline | Point during at which ventilation starts to increase at a faster rate than VO2 - derived from CPET |
| Ventilatory threshold 2 | Baseline | The point at which the oxygen demand of the muscles exceeds the ability of the cardiopulmonary system to supply oxygen- derived from CPET |
| Breathing reserve | Baseline | Difference between the maximal voluntary ventilation (MVV) and the maximum ventilation measured during CPET |
| Oxygen pulse | Baseline | The oxygen pulse is the oxygen (O2) divided by heart rate, and represents the product of the stroke volume and the arterial-venous oxygen difference. Derived from CPET. |
| Ventilatory equivalents for oxygen (VE/VO2) | Baseline | Ratio of the volume of gas expired per minute to the volume of oxygen consumed per minute- derived from CPET |
| Ventilatory equivalents for carbon dioxide(VE/VCO2) | Baseline | Ratio of the volume of gas expired per minute to the volume of carbon dioxide produced per minute- derived from CPET |
| Ventilatory equivalents for carbon dioxide (VE/VCO2) | 6 months post baseline | Ratio of the volume of gas expired per minute to the volume of carbon dioxide produced per minute- derived from CPET |
| Respiratory Exchange Ratio (RER) | Baseline | Ratio of carbon dioxide output/oxygen uptake (VCO2/VO2) at peak exercise intensity - derived from CPET |
| Blood lactate concentration | Baseline | Sampled from fingertip within 60 sec of CPET completion to assess level of anaerobic processes |
| C-Reactive protein | Baseline | Non-fasting blood samples are measured at the hospital laboratory and analysed for C-Reactive protein |
| Erythrocyte Sedimentation Rate | Baseline | Non-fasting blood samples are measured at the hospital laboratory and analysed for Erythrocyte Sedimentation Rate |
| Total cholesterol | Baseline | Non-fasting blood samples are measured at the hospital laboratory and analysed for total cholesterol |
| High-density lipoproteins | Baseline | Non-fasting blood samples are measured at the hospital laboratory and analysed for high-density lipoproteins |
| Low-density lipoproteins | Baseline | Non-fasting blood samples are measured at the hospital laboratory and analysed for low-density lipoproteins |
| Triglycerides | Baseline | Non-fasting blood samples are measured at the hospital laboratory and analysed for triglycerides |
| Blood pressure | Baseline | Supine systolic and diastolic blood pressure |
| Body Mass Index | Baseline | Weight in kilograms divided by the square of height in meters |
| Waist circumference | Baseline | Waist girth in centimeters. Measured in a standing position after a full exhale. |
| Dosage of medication | Baseline | Usage of medications last three months. Measured in dosage. |
| Psoriatic Arthritis Impact of Disease (PsAID) | Baseline | Patient-reported outcome measure for assessing psoriatic arthritis. Calculated based on 9 Numerical rating scales (NRS) questions regarding pain, fatigue, skin, work and/or leisure activities, function, discomfort, sleep, coping and anxiety. Each NRS is assessed as a number between 0 and 10. Range of final PsAID value is 0-10 where higher figures indicate worse status. Relevant for study participants with psoriatic arthritis. |
| Resting heart rate | Baseline | Recorded in conjunction with blood pressure measurement at rest- resting supine on a bench |
| Health-related quality of life, EuroQoL (EQ5D-5L) | Baseline | Health-related quality of life is measured by the EQ5D-5L questionnaire. Patients are asked to answer their ability to perform walking, personal care and activities of daily life on a 5 point Likert scale from no difficulties to not able to. Pain and anxiety/depression is measured on a 5 point Likert scale from no pain to very strong pain, and no anxiety/depression to extremely anxious/depressed. General experience of health is measured from 0 (worst health) to 100 (best health) on a numeric rating scale. |
| Frequency of medication | Baseline | Usage of medications last three months. Measured in frequency. |
| Self-reported fatigue | Baseline | Last week's experience of fatigue is measured on a Numeric rating scale from 0 (No fatigue) to 10 (Worst imaginable fatigue). |
| Self-reported pain | Baseline | Last week's experience of pain measured by numeric rating scale ranging from 0 (no pain) to 10 (worst imaginable pain). |
| Self-reported physical activity (HUNT) | Baseline | Measured by questions from the Nord-Trøndelag Health study (HUNT): average frequency (never/\<1 per week/1 per week/2-3 per week/almost every day), intensity (easy without losing my breath or breaking into a sweat/so hard that I lose my breath and break into a sweat/I push myself to near-exhaustion) and duration (less than 15 minutes/15-29 minutes/30 minutes to 1 hour/more than 1 hour) of physical activity. |
| SCORE2 | Baseline | Systemic Coronary Risk Estimation 2 Evaluation: Age, sex, smoking status, non-HDL blood cholesterol and systolic blood pressure is used to estimate 10-year risk of fatal and non-fatal cardiovascular disease. |
| Forced vital capacity | Baseline | Volume of air that can be forcefully exhaled after a full inspiration, measured in liters. Obtained from spirometry |
| Forced expiratory volume in 1 second (FEV1) | Baseline | Volume of air that can be forcefully exhaled in the first second after a full inspiration, measured in liters- obtained by spirometry |
| FEV1/FVC ratio | Baseline | Ratio (%) of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) |
| Forced expiratory flow | Baseline | Speed of air during the middle part of a forced expiration, intervals at 25%, 50% and 75% of exhaled FVC, measured in liter per second (L/s) - obtained by spirometry |
| Rheumatoid arthritis impact of disease (RAID) | Baseline | Patient-reported outcome measure for assessing rheumatoid arthritis. Calculated based on 7 Numerical rating scales (NRS) questions regarding pain, functional capacity, fatigue, physical wellbeing, emotional wellbeing, quality of sleep and coping. Each NRS is assessed as a number between 0 and 10. Range of final RAID value is 0-10 where higher figures indicate worse status. Relevant for study participants with rheumatoid arthritis. |
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | Baseline | Patient-reported outcome measure for assessing ankylosing spondylitis. Calculated based on 6 Numerical rating scales (NRS) questions regarding fatigue, pain, spinal pain, joint pain, pain on palpation of areas with localized tenderness, morning stiffness severity and morning stiffness duration. Each NRS is assessed as a number between 0 and 10. Range of final BASDAI value is 0-10 where higher figures indicate worse status. Relevant for study participants with spondyloarthritis. |
| Bath Ankylosing Spondylitis Functional Index (BASFI) | Baseline | Patient-reported outcome measure for assessing functional limitation in patients with ankylosing spondylitis. Calculated based on 10 Numerical rating scales (NRS) questions, 8 questions regarding functional limitations and 2 questions regarding the ability to cope with everyday life. Each NRS is assessed as a number between 0 and 10. Range of final BASFI value is 0-10 where higher figures indicate worse status. Relevant for study participants with spondyloarthritis. |
| Bath Ankylosing Spondylitis Global Score (BAS-G) | Baseline | Patient-reported outcome measure for assessing ankylosing spondylitis. Calculated based on 2 Numerical rating scales (NRS) questions regarding patients's well-being the previous week and previous six months. Range of final BAS-G value is 0-10 where higher figures indicate worse status. Relevant for study participants with spondyloarthritis. |
| Ankylosing Spondylitis Disease Activity Score (ASDAS) | 3 months post baseline | Composite score to assess disease activity in ankylosing spondylitis. Calculated based on three questions from BASDAI, patient global assessment on 0-10 scale and C-Reactive Protein or Erythrocyte Sedimentation Rate from blood samples. Relevant for study participants with spondyloarthritis. |
| Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28) | Baseline | Composite score to assess disease activity in rheumatoid arthritis. Calculated based on number of swollen (0-28) and tender joints (0-28), patient global assessment of health and C-Reactive Protein or Erythrocyte Sedimentation Rate from blood samples. Relevant for study participants with rheumatoid arthritis. |
| Disease Activity in PSoriatic Arthritis (DAPSA) | Baseline | Composite score to assess disease activity in psoriatic arthritis. Calculated based on number of swollen (0-66) and tender joints (0-68), patient global assessment of health and C-Reactive Protein or Erythrocyte Sedimentation Rate from blood samples. Relevant for study participants with psoriatic arthritis |
| Post-exercise questionnaire | 3 months post baseline | Electronic questionnaire distributed to patients in the experimental group upon completion of HIT intervention. 14 statements related to participation in the HIT exercise intervention and perceived intensity, duration and frequency of the exercise intervention. Scored on a 5 point Likert scale ranging from strongly disagree to strongly agree. |
| Use of healthcare services | Baseline | Use of health care services is measured by number of consultations to general practitioner, medical specialist, physiotherapist, occupational therapist, Healthy Life Centres, psychologist in the last three months. |
| Smoking status | Baseline | Registered by self-report; I smoke daily, I am a former smoker , I have never smoked |
| Snuff status | Baseline | Registered by self-report; I use snuff daily, I have previously used snuff, I have never used snuff |
| Peak heart rate | Baseline | Peak heart rate observed during CPET |
| Augmentation index | Baseline | Indicator of arterial stiffness, measured by mobil-o-graph at the same time as measure of blood pressure |
| Pulse Wave Velocity | Baseline | Measure of arterial stiffness- rate at which blood propagates through the vessels. Measured by moil-o-graph at the same time as measure of blood pressure |
| Exercise self-efficacy | Baseline | Measured by Exercise Beliefs and Exercise Habits questionnaire: comprises 20 items addressing exercise self-efficacy (4 items), barriers to exercise (3 items), benefits of exercise (5 items), and impact of exercise on arthritis (8 items), scored on a 5-point Likert scale ranging from strongly disagree to strongly agree. The scores on each subscale is summed up where higher scores indicate better self-efficacy. |
| Exercise frequency | 3 months post baseline | Participants in the experimental group are asked to record individual exercise session in a training diary. Exercise frequency is recorded. |
| Exercise intensity | 3 months post baseline | Participants in the experimental group are asked to record individual exercise session in a training diary. Exercise intensity is recorded by use of a herat rate monitor. |
| Exercise duration | 3 months post baseline | Participants in the experimental group are asked to record individual exercise session in a training diary. Exercise duration is recorded. |
| Peak expiratory flow (PEF) | Baseline | Maximum speed of expiration, expressed in liters per minute (L/min)- obtained from spirometry |
| Exercise-related adverse events | 3 months post baseline | Participants in the experimental group are asked to record individual exercise session in a training diary. Exercise-related adverse events are recorded. |
| Self-reported cardiovascular health and symptoms | Baseline | 13 yes/no questions regarding self-report of cardiovascular disease, symptoms and cardiac surgery. If the participant answers yes to preliminary question regarding angina, 5 ancillary questions pertaining to angina symptomatology are provided |
| Self-report change in physical fitness | 3 months post baseline | Patient global change in self-perceived physical fitness measured on a 5-point Likert scale ranging from much better to much worse |
| Self-report exercise habits | 3 months post baseline | Questionnaire; self-report of exercise habits from baseline to 3 months post baseline: Participation in regular exercise (yes/no), if yes: frequency (1-2 times/week, 3-4 times/week, 5 times or more/week) and mode of exercise (endurance exercise, strength exercise, mobility exercise and/or other). These questions are only forwarded to participants in the control group at this timepoint. Exercise habits form baseline to 3 months post baseline is recorded via the training diary for participants allocated to HIIT (experimental group): see outcome 153-157. |
| Corona virus 19 infection | 3 months post baseline | Questionnaire; self-report regarding corona virus 19 infection (yes/no, if yes: hospitalization/no hospitalization) from baseline to 3 months post baseline |
| Corona virus 19 quarantine | 3 months post baseline | Questionnaire; self-report regarding corona virus 19 quarantine (yes/no) from baseline to 3 months post baseline |
| Maximum minute ventilation at peak exercise (VEmax, L/min) | Baseline | Maximum ventilation, recorded from CPET at peak exercise |
| Early session termination | 3 months post baseline | Participants in the experimental group are asked to record individual exercise session in a training diary. Early session termination is recorded. |
Countries
Norway
Outcome results
None listed