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Effects of High-intensity Interval Training (HIIT) in Recent Onset Polymyositis and Dermatomyositis

Not Applicable
Conditions
Polymyositis
Dermatomyositis
Interventions
Other: Standard low-intensity home exercise
Other: High-intensity interval training (HIIT) - myositis
Other: High-intensity interval training (HIIT) - healthy
Registration Number
NCT03324152
Lead Sponsor
Karolinska University Hospital
Brief Summary

Polymyositis and dermatomyositis are rare inflammatory systemic conditions. Reduced muscle function is a cardinal symptom and lung involvement is very common. Knowledge of heart involvement in these patients is very limited, as is knowledge of exercise effects in recent onset, active disease.

The aim of this project is to investigate effects of high-intensity interval training (HIIT) compared to standard low-intensity home exercise as to tolerance, physical capacity, quality of life, depression, disease activity, inflammation, muscle mass/fat mass, muscle metabolism and heart function in patients with recent onset, active polymyositis and dermatomyositis.

This is a randomized controlled trial. Muscle biopsies are taken at time of diagnosis and after 12 weeks of exercise. Muscle biopsies will be analyzed as to baseline kynurenine pathway, calcium release, gene expression and inflammatory infiltrates and as to changes in these parameters following exercise. Muscle function (primary outcome), maximal oxygen uptake, muscle mass/fat mass, disease activity, systolic and diastolic heart function, as well as quality of life and depression is measured at baseline and after 12 weeks of exercise. After all assessments, patients are randomized to HIIT or standard low-intensity home exercise.

The HIIT group will perform 6 sets of 30-60 second biking bouts reaching 85-100% of maximal heart rate, in combination with strength training, three days a week for 12 weeks. The control group will perform a standardized home exercise program five days a week for 12 weeks. After 12 weeks, all assessments are preformed again. If the HIIT is well tolerated, patients in the control group will be invited to HIIT exercise according to the same protocol. Clinical assessments will be performed at 3, 6 and 9 months follow-up in an open extension.

This study will improve our understanding of heart function, muscle metabolism as well as tolerance and effects of intensive exercise as well as heart function early in the disease course and could also improve treatment and prognosis in patients with polymyositis and dermatomyositis.

Detailed Description

Patients randomized to the HIIT protocol will train three days a week for 12 weeks. Before exercise start participants will rate self-reported pain and fatigue on a visual analogue scale and describe in own words information about possible changes in medication dose, any side effects from medication as well as possible negative and positive effects from previous exercise sessions, as well as physical activities performed since the previous exercise session. Each exercise session starts with a 5-minut warm-up on about 50% of maximal heart rate. Each HIIT set is between 30-60 seconds where loads are increased and the participant bikes as fast as possible with the goal of reaching \>85% of maximal heart rate. During the 2-minuts rest in-between HIIT sets the participant will rate self-reported exertion using the Borg CR-10, 0-10 scale and the Borg RPE scale, 6-20.

When initiating the exercise period, participants start on three HIIT sets on a lower intensity, gradually increasing to goal intensity during the first two weeks. Then the number of sets are gradually increased to six sets.

After completing six HIIT sets the participants perform one set of 10 voluntary repetitions maximum (VRM) resistance training of the deltoids using free weights and of the quadriceps using free weights or a quadriceps curl machine, depending on degree of muscle weakness. Every other week a new 10 VRM is tested and training loads are adapted. After completing each set, the participant rates perceived muscle exertion on the Borg CR-10 scale. The program is ended with stretching of trained muscle groups and rating of overall exertion during the exercise session on the Borg RPE-scale.

Participants randomized to the control group will perform a standardized home exercise program on an easy-to moderate intensity adapted to initial muscle weakness, five days a week for 12 weeks. The program includes tasks for muscle groups targeted by myositis and takes about 15 minutes to perform. In combination with the home exercise program the participants walks 15 minutes on 60% of maximal heart rate. Participants fill out an exercise diary commenting on loads and number of repetitions for each task.

Participants in both groups ware a Polar 330A heart rate monitor during each training session. By synchronizing to a computer program all exercise data are stored in a cloud data base and can be monitored regularly by the project investigator.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Probable or definite diagnosis polymyositis or dermatomyositis according to Bohand and Peter criteria, diagnosis duration between 4 weeks and 6 months, completed screening for possible concurrent cancer diagnosis and screening for lung involvement, able to performe the HIIT.
Exclusion Criteria
  • Diagnosis of inclusion body myositis, active cancer, being treated for cancer, heart- or lung involvement contraindicating HIIT, no clinical improvement with medical treatment, severe osteoporosis.

Healthy controls:

Inclusion Criteria: match a patient for age and gender, exercising not more than twice a week, no neuro- or musculoskeletal disorders.

Exclusion Criteria: Ongoing treatment for cancer, cardiovascular disease contraindicating a maximal oxygen uptake test or HIIT.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard low-intensity home exercise control (CG)Standard low-intensity home exercise12-week, 5 d/w, home exercise.
High-intensity interval training (HIIT) - myositisHigh-intensity interval training (HIIT) - myositis12-week, 3d/w, HIIT
High-intensity interval training (HIIT) - healthyHigh-intensity interval training (HIIT) - healthy12-week, 3d/w, HIIT.
Primary Outcome Measures
NameTimeMethod
VO2 max, L/min and ml/kgxmin12 weeks

A maximal oxygen uptake test with ECG on a stationary bike. For patients with myositis, the test is started on 30W and increasing with 10W every minute until exhaustion. Ventilation and gas exchanges is assessed. Definition of max: ration CO2 / O2 = \>1. The test is stopped when maximal effort according to above definition is reached or when the subjects cannot bike any longer due to exhaustion. Healthy subjects will start on 50W and then follow the same protocol. Subjects rate subjective exertion of thigh muscles, dyspnea on the Borg symptom scale, 0-10. After completion of test overall exertion is rated on the Borg RPE scale, 6-20.

Secondary Outcome Measures
NameTimeMethod
Myositis Disease Activity Assessment Tool (MDAAT) - physician's global assessment.12 weeks

A myositis-specific protocol in Biodex systems is used. After completing measures of MVIC, the subjects perform six sets of 12, 4-second contractions with a 6-second rest in-between. Set 1: 12 contractions on 20% of MVIC. For each set, intensity is increased by 10%. In the last, 6th set contractions are performed on 70% of MVIC. After each set, a new MVIC is tested. The MDAAT is a valid core set of measures to assess disease activity including physician's and patient's global assessment, measures of muscle strength, activity limitation and extra-muscular organ activity. Physician's global assessment is performed in a Visual Analogue Scale (VAS), 0-100.

Myositis Disease Activity Assessment Tool (MDAAT) - patient's global assessment12 weeks

The MDAAT Patient's global assessment is performed in a Visual Analogue Scale (VAS), 0-100.

Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT constitutional12 weeks

The MDAAT, MYOACT constitutional (fever, weight loss) is assessed on a VAS, 0-100.

Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skin12 weeks

The MDAAT, MYOACT skin involvement (skin rash) is assessed on a VAS, 0-100.

Inflammatory infiltrates in skeletal muscle12 weeks

Muscle biopsies are analyzed for inflammatory infiltrates with immunohistochemistry.

Aerobic capacity, Watt max12 weeks

A maximal oxygen uptake test with ECG on a stationary bike. For patients with myositis, the test is started on 30W and increasing with 10W every minute until exhaustion. Ventilation and gas exchanges is assessed. Definition of max: ration CO2 / O2 = \>1. The test is stopped when maximal effort according to above definition is reached or when the subjects cannot bike any longer due to exhaustion. Healthy subjects will start on 50W and then follow the same protocol. Subjects rate subjective exertion of thigh muscles, dyspnea on the Borg symptom scale, 0-10. After completion of test overall exertion is rated on the Borg RPE scale, 6-20.

Myositis Disease Activity Assessment Tool (MDAAT) - Health Assessment Questionnaire (HAQ).12 weeks

The MDAAT, HAQ includes 20 questions about ability to perform daily activities with a composite score varying from 0-3, where 3 indicates severe limitations.

Myositis Disease Activity Assessment Tool (MDAAT) - serum creatine phosphokinase (CK).12 weeks

The MDAAT, serum CK-levels is measured in mikrocat/L.

Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT lung12 weeks

The MDAAT, MYOACT lung involvement is assessed on a VAS, 0-100.

Myositis Damage Index (MDI) - lung6 months

Degree of lung dagame is assessed on a VAS, 0-100

Myositis Damages Index (MDI) Skeletal6 months

Degree of joint damage and osteoporosis is assessed on a VAS, 0-100.

Isometric muscle strength12 weeks

A myositis-specific protocol in Biodex systems is used. Following several familiarization sets, maximal voluntary isometric contraction (MVIC) is tested until three very similar contractions are recorded. The subjects rest one minute between each MVIC.

Myositis Disease Activity Assessment Tool (MDAAT) - Manual Muscle Test12 weeks

The MDAAT Manual muscle test measures isometric muscle strength in 8 muscle groups with a composite score varying from 0-80, where 8 indicates good muscle strength.

Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT heart12 weeks

The MDAAT, MYOACT heart involvement is assessed on a VAS, 0-100.

Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT gasto-intestinal tract.12 weeks

The MDAAT, MYOACT gastro-intestinal tract involvement such as dysphagia is assessed on a VAS, 0-100.

Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skeletal12 weeks

The MDAAT, MYOACT skeletal (joint inflammation and bone density) involvement is assessed on a VAS, 0-100.

ER-stress12 weeks

Muscle biopies are analysed by ELIZA

Proteins involved in kynurenine process12 weeks

Muscle biopsies are analyzed by ELIZA

Proteins involved in calcium release12 weeks

Muscle biopsies are analyzed by ELIZA

Isomteric muscle fatigability12 weeks

A myositis-specific protocol in Biodex systems is used. After completing measures of MVIC, the subjects perform six sets of 12, 4-second contractions with a 6-second rest in-between. Set 1: 12 contractions on 20% of MVIC. For each set, intensity is increased by 10%. In the last, 6th set contractions are performed on 70% of MVIC. After each set, a new MVIC is tested.

Myositis Damage Index (MDI) - muscle6 months

Degree of skeletal muscle damage is assessed on a VAS, 0-100

Myositis Damage Index (MDI) gastro-intestinal tract6 months

Degree of GI-tract damage is assessed on a VAS, 0-100.

Myositis Damage Index (MDI) heart6 months

Degree of damage of the heart is assessed on a VAS, 0-100.

Stress echocardiography12 weeks

Systolic and diastolic heart function is assessed by ultrasound of the heart.

Gene expression12 weeks

Muscle biopsies are analyzed with Micro Array technique

Trial Locations

Locations (1)

Karolinska University Hospital

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Stockholm, N/A = Not Applicable, Sweden

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