Clinical trial NCT03324152: Effects of High-intensity Interval Training (HIIT) in Recent Onset Polymyositis and Dermatomyositis
Official title: Effects of High-intensity Interval Training (HIIT) Compared to Low-intensity Exercise in Patients With Recent Onset Polymyositis and Dermatomyositis - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Polymyositis
Dermatomyositis
Keywords: High-intensity interval training
Exercise
Muscle function
Inflammation
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
First posted: 2017-10-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are dandomized to either a high-intensity interval group (HIIT) or a control group performing standard low-intensity home exercise.
Primary purpose: TREATMENT

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.

Eligibility criteria: Patients with polymyositis and dermatomyositis:

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.

Primary outcomes:
measure: VO2 max, L/min and ml/kgxmin
timeFrame: 12 weeks
Secondary outcomes:
measure: Aerobic capacity, Watt max
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - physician's global assessment.
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - patient's global assessment
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - Manual Muscle Test
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - Health Assessment Questionnaire (HAQ).
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - serum creatine phosphokinase (CK).
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT constitutional
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT heart
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT lung
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skeletal
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT gasto-intestinal tract.
timeFrame: 12 weeks
measure: Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skin
timeFrame: 12 weeks
measure: Myositis Damage Index (MDI) - muscle
timeFrame: 6 months
measure: Myositis Damage Index (MDI) - lung
timeFrame: 6 months
measure: Myositis Damage Index (MDI) gastro-intestinal tract
timeFrame: 6 months
measure: Myositis Damages Index (MDI) Skeletal
timeFrame: 6 months
measure: Myositis Damage Index (MDI) heart
timeFrame: 6 months
measure: Stress echocardiography
timeFrame: 12 weeks
measure: Inflammatory infiltrates in skeletal muscle
timeFrame: 12 weeks
measure: Gene expression
timeFrame: 12 weeks
measure: ER-stress
timeFrame: 12 weeks
measure: Proteins involved in kynurenine process
timeFrame: 12 weeks
measure: Proteins involved in calcium release
timeFrame: 12 weeks
measure: Isometric muscle strength
timeFrame: 12 weeks
measure: Isomteric muscle fatigability
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
state: N/A = Not Applicable
Study officials:
affiliation: Karolinska University Hospital and Karolinska Institutet
name: Helene Alexanderson, PhD, Ass.Prof
role: PRINCIPAL_INVESTIGATOR
References:
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