Aerobic Exercise Program Followed by Cold Water Immersion: Effects on Arthritis Patients Arterial Stiffness
Condition: Rheumatoid Arthritis; Cryotherapy Effect; Physical Activity
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional

Summary: 
      The purpose of this study is to analyze the long-term effects of a physical exercise program
      on the cardiovascular system of people with Rheumatoid Arthritis (RA).

      Indeed, it is recognized that RA patients have cardiovascular problems and that regular
      physical exercise (exercise training) may be beneficial for the disease complications,
      incluse the cardiovascular risk. Unfortunately, these patients do not exercise enough for
      fear of joint pain or for fear of deteriorating their general physical condition.

      It is known that intermittent exercises, ie combining low and high intensity work phases, are
      particularly effective in the cardiovascular field. As it is possible that the high intensity
      phases be more difficult to sustain than the low intensity phases (joint pain and degradation
      of the inflammatory status), the investigators propose to study the effects of cold water
      immersion in the legs after performing this exercise, because the cold being recognized as
      limiting the pain and improving the inflammatory status.
    

Detailed description: 
      The first visit or selection visit, will be the opportunity for the investigator to submit
      the Information Notice and Informed Consent about. A second visit or visit of inclusion will
      be the occasion of the return of the signed informed consent of the subject. This visit will
      include a clinical examination for the detection of a pathology likely to contraindicate the
      practice of a physical activity and a resting electrocardiogram. The investigator will record
      the data for each subject, and check the eligibility criteria. Patient's treatments will not
      be interrupted throughout the program.

      The typical rehabilitation sessions will be performed according to the intermittent exercise
      followed by a cold water immersion recovery at 17 ° Celsius for 15 minutes. The total
      duration of the rehabilitation session will be approximately 50 minutes and the sessions
      should be separated by at least 48 hours with a frequency of 3 sessions per week by 6 weeks,
      totalizing 17 sessions.

      The typical sessions will be conducted as follows: intermittent exercise on a cycle ergometer
      for 30 minutes in sub-maximal intensity; application of the BORG scale; immersion in cold
      water at 17 ° C for 15 minutes and application of the cold water tolerance scale. The
      subject's heart rate will be recorded continuously for the duration of the sessions by a
      heart rate monitor (Polar Electro, Finland).

      Intermittent exercise consists of six 5-minute cycles with a succession of work (high: 1
      minute, moderate: 4 minutes). The high intensity work phase will be adjusted to achieve a
      target Heart Rate (HR) corresponding to HR rest + 70% HR reserve (HR reserve = (200 - age) -
      HR rest). The low intensity work phase will be adjusted to achieve a maximum target HR
      corresponding to HR rest + 50% HR reserve. In total, the exercise has a sub maximal
      intensity, commonly used in exercise rehabilitation studies conducted on various pathologies.
      It is an intensity capable of promoting cardiovascular benefits without representing a severe
      intensity for the patient.

      The target intensity for intermittent work is controlled by monitoring the HR. To achieve the
      desired , patients will be asked to adjust their pedaling frequency. The patient therefore
      adapts his pedaling frequency in accordance with the target HR to switch from one workload to
      another. During the rehab sessions, the wattage and pedaling frequency will be recorded. The
      cycloergometer used will be of the brand Monark (type 839E).

      Measurements will be made before, in the middle and at the end of the program (before 1st,
      10th and after 17th session (S1, S10 & S17). These examinations are commonly performed in the
      follow-up of rheumatoid arthritis:

        1. / The blood sample will be taken at the elbow crease by a clinical research nurse. There
           will be a total of three blood samples of approximately 7 mL of blood for subjects who
           are doing the entire program and only two blood tests for other subjects. Venous blood
           samples will be used to determine serum marker concentrations of C-reactive protein
           inflammation. The investigators will also perform the assay of two other blood markers
           of IL-6 inflammation and TNF-alpha classically used in the clinical follow-up of this
           kind of patient.

        2. / The clinical examinations will consist in the evaluation of the DAS-28 as well as an
           ultrasound of the joints. The Disease Activity Score (DAS) and its derivatives have been
           developed and validated by Dutch authors and considered the best test for the RA
           classification by the European League Against Rheumatism (EULAR). Several studies have
           shown that there is a very good correlation between the evaluation of RA activity on
           only 28 joints compared to 44 or 66. DAS-28 includes pain rating for joint pressure and
           joint swelling on the proximal interphalangeal (PPI), metacarpophalangeal (MCP) joints
           of the hands, wrists, elbows, shoulders, and knees. DAS-28 has the advantage of being
           more quickly achieved and of not rating rare joints such as distal interphalangeal or
           temporomandibular. It is however often criticized because it does not evaluate the
           joints of the feet which are on the contrary very frequently painful or inflammatory in
           this disease. Nevertheless, DAS-28 is currently the most frequently used score for the
           assessment of RA activity, whether in clinical studies or in routine practice.

           The articular ultrasound will be performed with an ESAOTE mylab five device on 32 joints
           of the hands, wrists and feet using a qualitative synovitic score in B mode and Doppler
           mode, each rated from 0 to 32, for a total score ranging from 0 to 64.

        3. / The assessment of functional disability, physical activity and quality of life and
           well-being will be done using questionnaires: HAQ, SQUASH and SF-36.

           The Health Assessment Questionnaire (HAQ) is a tool to measure specific functional
           disability for rheumatoid arthritis. The evaluation covers 8 areas of daily activity.
           Four types of answers are possible: a score of 0 to 3, where "0" means the absence of
           disability, while a score of "3" corresponds to a maximum disability.

           The Short Questionnaire to Assess Helath Enhancing Physical Activity (SQUASH) is a
           questionnaire that assesses average energy expenditure over a week. The questions are
           grouped into four different themes: commuting activities (going back and forth between
           home and work / study), leisure activities, home activities, work activity. For each
           type of activity, it is therefore required to indicate the average time spent per day,
           the number of days per week and the intensity of effort felt among three possible
           choices (calm, moderate and intense). The set of reported activities is calculated by
           multiplying the average time (in minutes) for an activity by its intensity coefficient
           corresponding to MET intervals. All activity scores are then summed to give the total
           score.

           The short-form 36 (SF-36) will be used to assess the quality of life and well-being. The
           SF-36 consists of 36 items, 35 of which are grouped into 8 multi-item scales that
           measure physical functioning, physical role, body pain, general health, vitality, social
           functioning, emotional role and mental health. The 8 SF-36 scales are scored on a scale
           of 0-100, with higher scores indicating a better quality of life.

           During the first session (S1), the target intensity is controlled by monitoring the
           heart rate as described above. The wattage and pedaling frequency achieved during the
           first session (S1) will be reproduced for the other series of measurements (S9 and S17).

           The measurements will be carried out at the first session of the protocol (S1) and then
           every 3 rehabilitation sessions (S5, S9, S13 and S17). These sessions will have a total
           duration of approximately 75 minutes.

             -  (Before exercise) rest extended by 15 minutes; a first evaluation (arterial
                pressures, elasticity of large and small arteries and the velocity of the radial
                and distal pulse wave, cutaneous temperature, etc.) of about 7 minutes in the
                extended position.

             -  (After the exercise) second elongated evaluation identical to the previous
                evaluation. The time between the end of the exercise and the start of the
                measurement will be controlled and identical for all subjects and measurement
                series.

             -  (After immersion) Third evaluation in lying position identical to the previous
                evaluation. The time between the end of the immersion and the start of the
                measurement will be controlled and identical for all subjects and measurements.

           The measurements:

        4. / Assessment of arterial stiffness will be performed by analyzing the pressure wave (a)
           and measuring the velocity of the pulse wave (b).

           a / HDI Pulse WaveTM CR-2000 tonometry device (HDI Hyperdiagnostics Inc., Eagan,
           Minnesota, USA): measurement of brachial arterial pressures and assessment of compliance
           of large and small arteries. This device records the shape of the pulse wave at the
           level of the radial artery using a sensor placed on the wrist (non-invasive
           measurement): the analysis of the shape of this wave makes it possible to obtain
           information on the compliance blood. The sensor will be positioned at the radial site
           used for VOP measurement.

           The HDI device includes a brachial cuff that makes it possible to measure arterial
           pressures simultaneously with the measurement of arterial stiffness. The systolic and
           diastolic blood pressure values will be collected at each resting phase.

           b / The assessment of central arterial stiffness will be performed by measuring the
           pulse wave velocity on the carotid-femoral segment. The evaluation of the arterial
           stiffness of the territories concerned (legs) or not (arms) by the exercises, will be
           carried out by the respective measurements of the pulse wave velocity on the
           carotid-distal and carotid-radial segments. These evaluations are carried out using the
           complior system (Complior SP®, Artech Medical, Pantin, France).

        5. / The skin temperature at the level of the thigh and the arm using a probe for recording
           the skin temperature: probes MLT409 / A Skin Temperature Probe (transducer ML309
           Thermistor Pod - ADInstruments ) fixed on the skin by a hypoallergenic adhesive.

        6. / At the end of each exercise, the subject is called to refer to the perception scale
           Borg, 1998: it goes from 6 to 20 points (where 6 means: "No effort" and 20: "maximum
           effort" ), and to indicate to the operator the number that corresponds best to the
           perception of his effort. The Borg Scale provides information on the subject's
           subjective perception of different parameters, such as stress or pain.

        7. / The perception of cold water tolerance will be evaluated with the aid of a visual
           analogue scale (0-100 mm), at the first, fifth, tenth and fifteenth minute of submerged
           recovery.

      The patient can stop his participation at any time without justification and can ask all the
      information he wants to the investigator or the operator. In case of exacerbation of the
      disease in relation to the results of the DAS-28 scale, the patient will leave the study.

      The study may be stopped by decision of the competent administrative authority, the sponsor,
      the coordinating investigator.

      Each patient will be able to leave the study by decision of one of these parties but also by
      decision of a co-investigator or by decision of the interested person himself, according to
      the regulation and as it is mentioned in the consent .
    

Intervention name(s): Exercise followed cold water immersion
Intervention type(s): Other
Intervention description(s): Rehabilitation program of 17 sessions with 30 minutes of exercise followed by 15 minutes of submerged recovery at 17 ° C (3 sessions per week / 6 weeks).
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Rheumatoid Arthritis; Physical exercise; Cryotherapy; Pulse Wave Velocity