Effects of Blood-flow Restricted Exercise Compared to Standard Rehabilitation in Patients With Knee Osteoarthritis

Effects of Blood-flow Restricted Exercise Compared to Standard Rehabilitation in Patients With Knee Osteoarthritis

Effects of Low-intensity Blood-flow Restricted Exercise Compared to Standard Rehabilitation in Patients With Knee Osteoarthritis - a Randomized Controlled Trial

University of Southern Denmark, Gigtforeningen, Sygekassernes Helsefond, AP Moeller Foundation, Aase and Ejnar Danielsens Foundation, Praksisfonen, FAPS

The purpose of this study is to investigate the effect of low-intensity BFR exercise on joint pain, muscle mass, and mechanical muscle function compared to standard rehabilitering in adults with knee-OA.

Osteoarthritis (OA) is a common disease in Denmark with high socioeconomical costs. Representing the most widespread non-medical and non-operative treatment modality both internationally and in Denmark, knee-OA patients often are offered a combination of patient education, weight loss counseling and physical exercise. In Denmark the GLA:D (Good Life with osteoArthritis in Denmark) concept is a nationwide training paradigm which is a combination of education and supervised neuromuscular exercise (NEMEX). Physical exercise including conventional strength training has shown positive results on OA, however a large proportion of OA-patients are forced to refrain from this type of training to excessive joint- and muscle pain during and following the training sessions. A more joint protecting type of training (BFR = Blood-Flow Restricted exercise), which are performed using low training load (<30% of maximum load) and with a reduced blood flow to the working muscles, has shown similar results to conventional heavy strength training. Based on these observations BFR exercise seems to represent an attractive training modality in patients with knee-OA. The aim of the present study is to investigate the effect of low-intensity BFR exercise on joint pain, muscle mass, and mechanical muscle function compared to SR in adults with knee-OA. A second aim is to investigate if 12 weeks of training is more efficient compared to 8 weeks of training. Patients diagnosed with knee-OA are eligible to participate. Inclusion takes place via the Institute of Sportsmedicine (ISMC), and the Department of Physical and Occupational Therapy at Bispebjerg Hospital. Patients will be called in for a preparatory examination by one of the attending physicians. At the consultation a standard clinical assessment will be performed and the participant will be examined for meeting the explicit inclusion or exclusion criteria of the study. If the participant after receiving all oral and written information wishes to participate in the study, an informed consent will be obtained. Randomization procedures will be performed. A randomized controlled trial design with two groups; 1) BFR, and 2) Standard rehabilitation. A total sample size of 90 participants are needed when assuming a 10 % dropout. The intervention period will last 12 consecutive weeks with 2 weekly training sessions at several chosen physiotherapy clinics (standard rehabilitation) and at Bispebjerg Hospital (BFR). Participants in the standard rehabilitation group will be offered participation in the GLA:D programme supervised by GLA:D certified physiotherapists. The BFR group will be trained by instructors who are experienced in BFR exercise. Testing will take place before the intervention period, after 8 weeks of training and at the end of the intervention (12 weeks) except for the muscle biopsies which will take place before the intervention period and at the end (12 weeks). Patient-reported questionnaires will furthermore be assessed 6 months after the intervention period. Patients will be tested at Bispebjerg Hospital for a number of different outcome measures including joint- and muscle pain, functional level and mechanical muscle function (strength and muscle mass).

The BFR training intervention group will perform low load blood-flow restricted exercise. Training twice a week for 12 weeks. The group will also attend a two hours education lecture with osteoarthritis information.

The standard rehabilitation group will be offered participation in the Good Life with osteoArthritis in Denmark programme (GLA:D). The programme includes supervised team group training twice a week for 8 weeks and an education lecture. The GLA:D programme will be followed by 4 weeks of team group training continuing the exercises from the GLA:D programme.

The BFR group performs unilateral training with the knee-OA diagnosed leg first. BFR exercise is performed with a pneumatic cuff placed at the top of the thigh on the leg being trained. The cuff will be inflated to 60-80 % of the total arterial occlusion pressure (AOP). The participant will afterwards perform training of the knee extensors in a leg press exercise machine and a leg extension exercise machine with a load corresponding to 30 % of the maximal load (1RM = Repetition Maximum).

The GLA:D programme involves a circuit training program with four stations. Each station involves two to six exercises where the participants perform 10-15 repetitions over 2-3 sets, which depends on the participants pain- and functional level. Following the 8 weeks GLA:D programme, participants will continue 4 weeks of team group training performing similar neuromuscular lower limb exercises as for the first 8 weeks.

KOOS is a patient reported outcome instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Primary outcome will be an assessment of the Pain subscale as a total KOOS score has not been validated. A normalized score for the entire subscale will be calculated and reported, ranging from zero (extreme symptoms) to 100 (no symptoms).

KOOS is a patient reported outcome instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Primary outcome will be an assessment of the Pain subscale as a total KOOS score has not been validated. A normalized score for the entire subscale will be calculated and reported, ranging from zero (extreme symptoms) to 100 (no symptoms).

KOOS is a patient reported outcome instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Primary outcome will be an assessment of the Pain subscale as a total KOOS score has not been validated. A normalized score for the entire subscale will be calculated and reported, ranging from zero (extreme symptoms) to 100 (no symptoms).

KOOS is a patient reported outcome instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Primary outcome will be an assessment of the Pain subscale as a total KOOS score has not been validated. A normalized score for the entire subscale will be calculated and reported, ranging from zero (extreme symptoms) to 100 (no symptoms).

Quadriceps myofiber cross-sectional area will be measured using a GE Logiq E10 Logic View ultrasound to generate panoramic CSA images. Orientated in the axial-plane, the ultrasound probe is positioned perpendicularly, and a water-based gel is used to promote acoustic contact between the skin and the probe. The probe is moved manually with a slow and continuous movement from the lateral to the medial part of quadriceps along a marked line on the skin. The anatomical site for all measurements will be at 50% of the distance between the lateral condyle and greater trochanter of the femur.

PPT is measured by a handheld pain pressure algometer at three different locations bilaterally. Most painful area in the medial joint line, tibialis anterior, and the muscle belly of extensor carpi radialis.

MVIC of the knee extensors is obtained during static knee extension in a KinCom, isokinetic dynamometer, at a knee joint angle of 70 degrees (0 degrees = full knee extension).

RFD of the knee extensors is obtained during static knee extension in a KinCom, isokinetic dynamometer, at a knee joint angle of 70 degrees (0 degrees = full knee extension).

The 40m-FWT is a test of walking speed over short distances and changing direction during walking. It measures the total time it takes to walk 4 * 10 m excluding turns (m/s).

The 30-s CST is used for testing leg strength and endurance. The 30-s CST will be assessed using a chair (seat height: 43-44 cm) with armrests. The 30-s CST measures the number of sit-to-stand repetitions completed within 30-s.

The SCT involves ascending and descending 10 stairs measuring 18 cm rise / 92 cm width. Each participant is asked to ascend/descend the stairs at their ''natural'' pace (without resting). One trial to ascend and descend is timed and recorded electronically.

Muscle biopsies will be obtained for determination of important myocellular components (number of muscular stem cells). It will be assessed by obtaining needle biopsies (100-150 mg). The biopsies will be obtained unilaterally from the middle portion of the vastus lateralis muscle using the percutaneous needle biopsy technique of Bergström.

Muscle biopsies will be obtained for determination of important myocellular components (fiber area in diameter: μm2). It will be assessed by obtaining needle biopsies (100-150 mg). The biopsies will be obtained unilaterally from the middle portion of the vastus lateralis muscle using the percutaneous needle biopsy technique of Bergström.

Muscle biopsies will be obtained for determination of important myocellular components (number of myonuclei). It will be assessed by obtaining needle biopsies (100-150 mg). The biopsies will be obtained unilaterally from the middle portion of the vastus lateralis muscle using the percutaneous needle biopsy technique of Bergström.

Explosive lower limb muscle power will be assessed during a single-legged extensor power-rig. Subjects will be seated in the power-rig chair and pushes away the footplate connected to a flywheel as hard and fast as possible.

KOOS is a patient reported outcome instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). A normalized score for the total KOOS score will be calculated and reported, ranging from zero (extreme symptoms) to 100 (no symptoms).

At baseline (0 weeks), 8 weeks, 12 weeks (the end of the intervention period) and 6 months after the intervention period.

The Oxford Knee Score is a patient reported outcome measure that consists of 12 questions about an individual's level of function, activities of daily living and how they have been affected by pain over the preceding four weeks. Each question is scored from 0-4 where four is the best outcome and total scores range from 0 (poorest function) to 48 (maximal function).

At baseline (0 weeks), 8 weeks, 12 weeks (the end of the intervention period) and 6 months after the intervention period.

Inclusion Criteria: All participants must meet the American College of Rheumatology (ACR) criteria for OA 35. Visible OA on X-ray pictures (Kellgren & Lawrence grade 2-3). Unilateral pain and functional limitation for a minimum of 3 months. Be able to voluntarily (i.e. unassisted) perform a 90 degrees flexion in the knee. Be able to perform the machine exercise (knee extension) planned for the BFR training. Danish-speaking. No longer travel planned within the intervention period. Exclusion Criteria: Kellgren & Lawrence grade 4. Bilateral OA-symptoms. Prior knee- or hip alloplasty. Glucocorticosteroid injection in the knee within the last 6 months. Inflammatory arthritis. Known neurotic disease such as multiple sclerosis or peripheral neuropathy. Prior myocardial infarct or apoplexy, or chest pain during physical activity. Other health related or medical conditions which makes it impossible participate in the study. Furthermore, it is an exclusion criterium in the following conditions where use of pneumatic occlusion would be considered contraindicated: Peripheral vascular disease Excessive varicose veins Prior history of deep venous thrombosis Venous insufficiency causing edema in the lower legs Systolic blood pressure over 160 mmHg or under 100 mmHg

Department of Physical and Occupational Therapy / Institute of Sports Medicine Copenhagen, Bispebjerg Hospital

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