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

Dermatomyositis Clinical Trial

— HIITmyositis  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03324152
• Other study ID #: KarolinskaUH1
• Status: Recruiting
• Phase: N/A
• First received: October 5, 2017
• Last updated: April 20, 2018
• Start date: October 1, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: April 2018
• Source: Karolinska University Hospital
• Contact: Helene Alexanderson, PhD, Ass.prof
• Phone: +46 8 517745 96
• Email: helene.alexanderson[@]sll.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dermatomyositis
• Polymyositis

Intervention

Other:
• High-intensity interval training (HIIT) - myositis
12-weeks of 3 days/week HIIT. 6 sets of 30-60 seconds on 85-100% of maximal heart rate performed on a stationary bike followed by resistance training on 10 voluntary repetition maximum.
• Standard low-intensity home exercise
12 weeks of 5 days/week low-intensity resistance home exercise in combination with outdoor walks of 20 minutes.
• High-intensity interval training (HIIT) - healthy
12-weeks of 3 days/week HIIT. 6 sets of 30-60 seconds on 85-100% of maximal heart rate performed on a stationary bike followed by resistance training on 10 voluntary repetition maximum.

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm	N/A = Not Applicable

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska University Hospital	Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

References & Publications (8)

Alemo Munters L, Dastmalchi M, Andgren V, Emilson C, Bergegård J, Regardt M, Johansson A, Orefelt Tholander I, Hanna B, Lidén M, Esbjörnsson M, Alexanderson H. Improvement in health and possible reduction in disease activity using endurance exercise in patients with established polymyositis and dermatomyositis: a multicenter randomized controlled trial with a 1-year open extension followup. Arthritis Care Res (Hoboken). 2013 Dec;65(12):1959-68. doi: 10.1002/acr.22068. — View Citation

Alemo Munters L, Dastmalchi M, Katz A, Esbjörnsson M, Loell I, Hanna B, Lidén M, Westerblad H, Lundberg IE, Alexanderson H. Improved exercise performance and increased aerobic capacity after endurance training of patients with stable polymyositis and dermatomyositis. Arthritis Res Ther. 2013 Aug 13;15(4):R83. doi: 10.1186/ar4263. — View Citation

Alexanderson H, Munters LA, Dastmalchi M, Loell I, Heimbürger M, Opava CH, Lundberg IE. Resistive home exercise in patients with recent-onset polymyositis and dermatomyositis -- a randomized controlled single-blinded study with a 2-year followup. J Rheumatol. 2014 Jun;41(6):1124-32. doi: 10.3899/jrheum.131145. Epub 2014 May 1. — View Citation

Alexanderson H. Physical exercise as a treatment for adult and juvenile myositis. J Intern Med. 2016 Jul;280(1):75-96. doi: 10.1111/joim.12481. Epub 2016 Feb 8. Review. — View Citation

Cleary LC, Crofford LJ, Long D, Charnigo R, Clasey J, Beaman F, Jenkins KA, Fraser N, Srinivas A, Dhaon N, Hanaoka BY. Does computed tomography-based muscle density predict muscle function and health-related quality of life in patients with idiopathic inflammatory myopathies? Arthritis Care Res (Hoboken). 2015 Jul;67(7):1031-40. doi: 10.1002/acr.22557. — View Citation

Munters LA, Loell I, Ossipova E, Raouf J, Dastmalchi M, Lindroos E, Chen YW, Esbjörnsson M, Korotkova M, Alexanderson H, Nagaraju K, Crofford LJ, Jakobsson PJ, Lundberg IE. Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis. Arthritis Rheumatol. 2016 Jul;68(7):1738-50. doi: 10.1002/art.39624. — View Citation

Yamada T, Fedotovskaya O, Cheng AJ, Cornachione AS, Minozzo FC, Aulin C, Fridén C, Turesson C, Andersson DC, Glenmark B, Lundberg IE, Rassier DE, Westerblad H, Lanner JT. Nitrosative modifications of the Ca2+ release complex and actin underlie arthritis-induced muscle weakness. Ann Rheum Dis. 2015 Oct;74(10):1907-14. doi: 10.1136/annrheumdis-2013-205007. Epub 2014 May 22. — View Citation

Yamada T, Place N, Kosterina N, Ostberg T, Zhang SJ, Grundtman C, Erlandsson-Harris H, Lundberg IE, Glenmark B, Bruton JD, Westerblad H. Impaired myofibrillar function in the soleus muscle of mice with collagen-induced arthritis. Arthritis Rheum. 2009 Nov;60(11):3280-9. doi: 10.1002/art.24907. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VO2 max, L/min and ml/kgxmin	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.	12 weeks
Secondary	Aerobic capacity, Watt max	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.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - physician's global assessment.	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.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - patient's global assessment	The MDAAT Patient's global assessment is performed in a Visual Analogue Scale (VAS), 0-100.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - Manual Muscle Test	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.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - Health Assessment Questionnaire (HAQ).	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.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - serum creatine phosphokinase (CK).	The MDAAT, serum CK-levels is measured in mikrocat/L.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT constitutional	The MDAAT, MYOACT constitutional (fever, weight loss) is assessed on a VAS, 0-100.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT heart	The MDAAT, MYOACT heart involvement is assessed on a VAS, 0-100.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT lung	The MDAAT, MYOACT lung involvement is assessed on a VAS, 0-100.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skeletal	The MDAAT, MYOACT skeletal (joint inflammation and bone density) involvement is assessed on a VAS, 0-100.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT gasto-intestinal tract.	The MDAAT, MYOACT gastro-intestinal tract involvement such as dysphagia is assessed on a VAS, 0-100.	12 weeks
Secondary	Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skin	The MDAAT, MYOACT skin involvement (skin rash) is assessed on a VAS, 0-100.	12 weeks
Secondary	Myositis Damage Index (MDI) - muscle	Degree of skeletal muscle damage is assessed on a VAS, 0-100	6 months
Secondary	Myositis Damage Index (MDI) - lung	Degree of lung dagame is assessed on a VAS, 0-100	6 months
Secondary	Myositis Damage Index (MDI) gastro-intestinal tract	Degree of GI-tract damage is assessed on a VAS, 0-100.	6 months
Secondary	Myositis Damages Index (MDI) Skeletal	Degree of joint damage and osteoporosis is assessed on a VAS, 0-100.	6 months
Secondary	Myositis Damage Index (MDI) heart	Degree of damage of the heart is assessed on a VAS, 0-100.	6 months
Secondary	Stress echocardiography	Systolic and diastolic heart function is assessed by ultrasound of the heart.	12 weeks
Secondary	Inflammatory infiltrates in skeletal muscle	Muscle biopsies are analyzed for inflammatory infiltrates with immunohistochemistry.	12 weeks
Secondary	Gene expression	Muscle biopsies are analyzed with Micro Array technique	12 weeks
Secondary	ER-stress	Muscle biopies are analysed by ELIZA	12 weeks
Secondary	Proteins involved in kynurenine process	Muscle biopsies are analyzed by ELIZA	12 weeks
Secondary	Proteins involved in calcium release	Muscle biopsies are analyzed by ELIZA	12 weeks
Secondary	Isometric muscle strength	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.	12 weeks
Secondary	Isomteric muscle fatigability	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.	12 weeks