Short summary

Low-intensity blood-flow restricted exercise is a potent trigger of muscle growth and activation of muscle stem cells. Sporadic inclusion body myositis causes severe atrophy of the skeletal muscle of the thigh and the forearm, which leads to decreased physical function and patient-reported health.

The purpose of this study is to investigate if low-intensity blood-flow restricted exercise can improve the patient-reported health and physical function of patients diagnosed with sporadic inclusion body myositis, in a parallel group randomised controlled study design.

Rationale

Sporadic inclusion body myositis (sIBM) is the most common inflammatory myopathy. It causes substantial deterioration of the peripheral skeletal muscle, which leads to muscle weakness and decreased functional capacity. In time the decreased physical function becomes so severe that it affects the patient's ability to perform even basic everyday tasks and result in dependency of other people on a daily basis. Currently no effectual treatment exists for sIBM.

Our research group have recently found a strong effect of low-intensity resistance exercise (20%1RM) with simultaneous restriction of blood flow through the working muscles (Blood-flow restricted (BFR)-exercise). The muscle generating effect of BFR-exercise was even greater than what is normally observed with conventional high-intensity resistance training (70-90%1RM). The low training loads render this exercise modality useful in a series of patients with physical impairments in which conventional high-intensity resistance training is not possible, but with the same effect on muscle generation.

The purpose of this study is to investigate if low-intensity blood-flow restricted exercise can improve the patient reported health and physical function of patients diagnosed with sporadic inclusion body myositis, in a parallel group randomised controlled study design.

Preliminary pilot data obtained from training with one patient indicates that the training is not only tolerated by the patients but also induce substantial improvements in neuromuscular function and functional capacity.

Description of the cohort

Participants will be recruited from the Region of Southern Denmark. 38 patients with clinically defined sIBM are identified in the hospital database:

Clinically defined sIBM.

• Duration of weakness > 12 months
• Age > 35 years
• Weakness of finger flexion > shoulder abduction AND knee extension > hip flexion
• Invasion of non-necrotic fibres by mononuclear cells or rimmed vacuoles
• Increased MHC-I but no amyloid deposits or 15-18nm filaments 

Patients with lacking gait function will not be invited to participate in the study because they will not be able to complete the training and test protocols outlined in this study. Of the patients invited to the study, those who accept to participate will undergo a medical examination to make sure they are fit to enter the study. Exclusion criteria are:

• Co-morbidity contraindicating the use of BFR-training (previous deep vein thrombosis/pulmonary embolism or known peripheral ischemic disease)
• Co-morbidity preventing resistance training (severe heart/lung-disease, uncontrolled hypertension (systolic > 160mmHg, diastolic > 100mmHg), severe knee/hip arthritis)

Data and biological material

Surveys:

• Short form (36) health survey (SF-36)
• Health assessment questionnaire (HAQ)
• Inclusion body myositis functional rating scale (IBMFRS)
• Myositis disease activity score (MITAX)
• Myositis damage index (MDI)
• Global activity/damage score

Functional measures

• 2-min walk test
• Timed Up & Go
• Manual Muscle Testing, MMT-8
• Sway - postural balance

Neuromuscular function

• Leg extension muscle power
• Maximal isometric knee extensor muscle strength (MVC) and rate of force development (RFD)
• Isokinetic knee extensor muscle strength (60° * s^-1)
• Central activation (Superimposed twitch, twitch interpolation)

Body composition

• Dual-Energy X-ray absorptiometry (DXA)

Biological material

• Muscle biopsies before and after intervention
• Fibre type distribution and fibre size
• Capillary density
• Myogenic stem cell activation
• Cellular inflammation
• Blood samples before and after intervention
• Creatine kinase, lactate dehydrogenase, c-reactive protein, creatinine and alanine aminotransferase

Collaborating researchers and departments

Department of Pathology, Odense University Hospital

• Professor Henrik Daa Schrøder, MD, PhD

Rheumatology Unit, Karolinska Institute, Sweden

• Professor Inger Lundberg, MD, PhD