This study is investigating whether a six-week exercise training programme, designed for patients with Rheumatoid Arthritis, improves disease activity, inflammation, cardiorespiratory fitness, muscle strength, flexibility and risk factors for cardiovascular disease. Twenty four patients will be randomly assigned to an intervention or control group (n=12 in each group). The intervention group will will undertake a fully supervised structured exercise training programme, consisting of both aerobic and strength training exercise, taking the form of two 70-minute group fitness classes per week for six weeks. These participants will also undertake a 30-minute walk in their own time. The control group will continue to go about their normal daily activities. Measurements will be made before and after the intervention/control period, including assessments of disease activity (e.g., by gauging how swollen and tender patients' joints are using the Disease Activity Score(DAS) ) and assessments of fitness and/or physical functioning (e.g., 200 meter timed walk test, a strength test, a flexibility test, Health Assessment Questionnaire Disability Index (HAQDI)). Blood samples will also be collected from patients before and after the intervention/control period to measure markers of inflammation, such as C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR). The investigators will also measure other parameters that are linked to type II diabetes (e.g., fasting glucose concentration) and factors implicated in cardiovascular disease risk (e.g., lipid profile and resting blood pressure).

Rheumatoid Arthritis (RA) is a multi-system autoimmune disease characterised by chronic inflammation (i.e., a persistent and inappropriate immune response). It primarily affects the joints, causing swelling, pain, reduced muscle strength and high biomarkers of inflammation such as C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). This immune response also results in accelerated atherosclerotic processes, decreased Bone Mineral Density (BMD) and damage to cartilage in the affected joints. Until the mid-1990s, patients with RA had traditionally been advised to avoid physical exercise, due to concerns it may result in progression of joint damage; hospital admission for bed rest was common practice. However, in the last 20 years, studies have shown that combined moderate-intensity aerobic exercise and strength training, can improve joint swelling, increase cardiorespiratory fitness and strength, without exacerbating pain or joint damage in patients with RA. Thus, the American College of Sports Medicine (ACSM) recommends that patients with RA walk or cycle for at least 30 minutes three times a week at a moderate intensity of 60% to 85% of maximum heart rate (HRmax) to improve cardiorespiratory fitness. The ACSM also recommends static or dynamic strength training of all large muscle groups twice weekly, performing three sets of 8-10 repetitions of 50% to 80% of one repetition maximum (1RM). While it is now established that exercise training can limit disease activity, and lower systemic inflammation, it is unclear whether short (e.g., six-weeks) and feasible exercise training programmes (e.g., two 70 minute sessions per week) elicit the same effects as the commonly employed interventions that are more demanding (e.g., 3-12 months; 3-5 sessions per week). In addition, it is unclear whether such a short intervention can modify other factors implicated in non-communicable disease, such as type II diabetes and cardiovascular risk (e.g., glucose control, lipid profile, blood pressure).

Objectives:

To examine if a six-week moderate intensity aerobic exercise and muscle strengthening programme:

• Results in changes in disease activity.
• Improves cardiorespiratory fitness, strength and flexibility.
• Reduces disease related inflammatory markers.
• Reduces blood pressure, improves lipid profile and improves glucose control.

Study Design:

Twenty-four patients will be randomised to either the exercise intervention (n= 12) or the control group (n = 12). The exercise intervention will consist of combined aerobic and strength training group-exercise intervention lasting six weeks, with two classes per week. All participants will undergo assessments to measure markers of inflammation, disease activity, physical fitness, strength, flexibility and cardiovascular risk factors before and after the six-week intervention.

Recruitment:

Female patients aged 18 to 69 years of age with RA attending Rheumatology outpatient clinics at the Belfast and Social Health Care Trust hospitals will be invited to participate. Patients satisfying the inclusion and exclusion criteria who would like to take part will attend two appointments before being randomised to either the six-week exercise intervention or the control group. Following the six-week intervention all patients will return for two further appointments to repeat all measurements taken before the intervention.

Measurements before the six-week intervention.

• Experimental Visit One. This visit is scheduled between 08:00-09:00 (duration 1 hour). Following written consent blood samples, blood pressure, anthropometry, joint examination, questionnaires will be carried out. All patients, in both groups, will be advised to arrive fasted with their last meal to have been eaten greater than 12 hours before arrival. Patients should refrain from exercise during the 48 hours before, and abstain from alcohol and caffeine for 24 hours.
• Experimental Visit Two. This visit is scheduled between 12:00-16:00 (duration 1 hour) and will consist of a 200 metre walk test, a sit and reach flexibility test, and strength test.

Measurements after the six-week intervention:

• Experimental Visit Three. This visit is scheduled between 08:00-09:00 (duration 1 hour). It is identical to visit one. Measurements include a blood sample, blood pressure, anthropometry, joint examination, questionnaires. All participants in both groups will be advised to arrive fasted with their last meal to have been eaten at least 12 hours before arrival. Patients should refrain from exercise during the 48 hours before, and abstain from alcohol and caffeine for 24 hours.
• Experimental Visit Four. This visit is scheduled between 12:00-16:00 (duration 1 hour) it is identical to visit two and consists of the 200 metre walk test, a sit and reach flexibility test, and strength test.

Exercise Intervention:

The six-week exercise programme will comprise two 70-minute group exercise classes per week (usually 12 patients per class). Classes will be fully supervised and will be conducted at a fitness and rehabilitation gymnasium. Each class will consist of four parts (A-D, see below). Participants will also be asked to go for a moderate intensity walk once a week for 30 minutes and maintain an exercise diary for all exercises including gym sessions.

A. Warm up and stretching for five minutes:

The warm-up will begin with standing and raising knees alternately for 30 seconds followed by gentle stretching of all the large muscles groups: lumbar, quadriceps, hamstrings, groin, pectorals, triceps, biceps, hands and feet muscles; stretching of each group will last for 30 seconds. Stretches will be modified for each patient and supportive props used where necessary.

B. Aerobic exercise for 30 minutes:

Aerobic exercise will consist of 30 minutes cycling on a stationary cycle ergometer. This will begin with a five-minute, low-intensity warm-up (low intensity is Heart Rate(HR) < 50% of age predicted HRmaximum). Intensity will then increase to 60% HRmax for 20 minutes, ending with a five-minute low intensity cool-down.

The exercise programme will be progressive, each week increasing in intensity by 5% of HRmax up to 85% HRmax during the final week. Patients will wear a wrist and chest heart-rate monitor, and will be advised when they have reached required intensity. This will be recorded at each class in their exercise diary along with minutes cycled. Progression of intensity will begin after week two to allow for familiarisation with the programme.

C. Strengthening exercises for 30 minutes:

This will consist of five exercises, working the large muscles of the upper limbs, lower limbs and abdomen: leg extension, bench press, low row, modified abdominal crunch and wall squat. Leg extension and low row will be performed on a pulley weights machine and bench press using the multi-gym system.

One repetition maximum (RM) is the maximum weight in kilograms that can be lifted once and no more. Each of these exercises will start with three sets of 8-10 repetitions at 60% of 1RM, progressing by 5% of 1RM each week. RM will be recalculated weekly after week two. Modified abdominal crunch will begin by assessing the maximum number of crunches the patient can perform to near exhaustion. The participants will then perform this number two more times with a 90 second rest in between. After two weeks this will be progressed by recalculating the number of crunches to near exhaustion each week.

The wall squat will start with assessment of the time the patient can hold the squat before becoming fatigued. This will be repeated twice more, with a 90 second rest in between. After two weeks this will be progressed by re-timing the wall squat until fatigue, each week thereafter.

A record of all exercises performed, along with weights lifted, times, and heart rate will be documented weekly by each patient in their record sheets.

D. Cool-down:

Five minutes of light stretching of all the large muscle groups and instructions on performing moderate intensity walk each weekend. The cooI-down is identical to the warm-up.

Inclusion Criteria:

• Female
• Age 18-69
• Non-smokers
• Diagnosis of Rheumatoid Arthritis for greater than 12 months
• Stable Disease modifying medication for the preceding three months
• Functional capacity class I-II
• Able to use an exercise bicycle
• Willing to exercise twice-weekly on a fixed schedule
• Available for eight weeks between May and September 2016

Exclusion Criteria:

• Cardiovascular disease (i.e. coronary heart disease, previous heart attack, angina, stroke or uncontrolled hypertension)
• Major psychiatric illness, such as schizophrenia or major depression
• A prosthetic hip or knee joint.