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

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 95 participants are needed when assuming a 20 % 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).

Eligibility Criteria:
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