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

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ClinicalTrials.gov Identifier: NCT03324152
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : April 23, 2018
Sponsor:
Collaborator:
Karolinska Institutet
Information provided by (Responsible Party):
Helene Alexanderson, Karolinska University Hospital

Tracking Information
First Submitted Date  ICMJE October 5, 2017
First Posted Date  ICMJE October 27, 2017
Last Update Posted Date April 23, 2018
Actual Study Start Date  ICMJE October 1, 2017
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2018)
VO2 max, L/min and ml/kgxmin [ Time Frame: 12 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
  • Isometric muscle strength [ Time Frame: 12 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.
  • Isometric muscle endurance [ Time Frame: 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.
Change History Complete list of historical versions of study NCT03324152 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2018)
  • Aerobic capacity, Watt max [ Time Frame: 12 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) - physician's global assessment. [ Time Frame: 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 assessment [ Time Frame: 12 weeks ]
    The MDAAT Patient's global assessment is performed in a Visual Analogue Scale (VAS), 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - Manual Muscle Test [ Time Frame: 12 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) - Health Assessment Questionnaire (HAQ). [ Time Frame: 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). [ Time Frame: 12 weeks ]
    The MDAAT, serum CK-levels is measured in mikrocat/L.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT constitutional [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT constitutional (fever, weight loss) is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT heart [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT heart involvement is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT lung [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT lung involvement is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skeletal [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT skeletal (joint inflammation and bone density) involvement is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT gasto-intestinal tract. [ Time Frame: 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 skin [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT skin involvement (skin rash) is assessed on a VAS, 0-100.
  • Myositis Damage Index (MDI) - muscle [ Time Frame: 6 months ]
    Degree of skeletal muscle damage is assessed on a VAS, 0-100
  • Myositis Damage Index (MDI) - lung [ Time Frame: 6 months ]
    Degree of lung dagame is assessed on a VAS, 0-100
  • Myositis Damage Index (MDI) gastro-intestinal tract [ Time Frame: 6 months ]
    Degree of GI-tract damage is assessed on a VAS, 0-100.
  • Myositis Damages Index (MDI) Skeletal [ Time Frame: 6 months ]
    Degree of joint damage and osteoporosis is assessed on a VAS, 0-100.
  • Myositis Damage Index (MDI) heart [ Time Frame: 6 months ]
    Degree of damage of the heart is assessed on a VAS, 0-100.
  • Stress echocardiography [ Time Frame: 12 weeks ]
    Systolic and diastolic heart function is assessed by ultrasound of the heart.
  • Inflammatory infiltrates in skeletal muscle [ Time Frame: 12 weeks ]
    Muscle biopsies are analyzed for inflammatory infiltrates with immunohistochemistry.
  • Gene expression [ Time Frame: 12 weeks ]
    Muscle biopsies are analyzed with Micro Array technique
  • ER-stress [ Time Frame: 12 weeks ]
    Muscle biopies are analysed by ELIZA
  • Proteins involved in kynurenine process [ Time Frame: 12 weeks ]
    Muscle biopsies are analyzed by ELIZA
  • Proteins involved in calcium release [ Time Frame: 12 weeks ]
    Muscle biopsies are analyzed by ELIZA
  • Isometric muscle strength [ Time Frame: 12 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.
  • Isomteric muscle fatigability [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
  • VO2max, L/min [ Time Frame: 12 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 can not bika any longer due to exhaustion. healthy sibjects 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.
  • VO2max, ml/kgxmin [ Time Frame: 12 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 can not bika any longer due to exhaustion. healthy sibjects 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.
  • Aerobic capacity, Watt max [ Time Frame: 12 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 can not bika any longer due to exhaustion. healthy sibjects 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) - physician's global assessment. [ Time Frame: 12 weeks ]
    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 assessment [ Time Frame: 12 weeks ]
    The MDAAT Patient's global assessment is performed in a Visual Analogue Scale (VAS), 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - Manual Muscle Test [ Time Frame: 12 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) - Health Assessment uestionnaire (HAQ). [ Time Frame: 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). [ Time Frame: 12 weeks ]
    The MDAAT, serum CK-levels is measured in mikrocat/L.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT constitutional [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT constitutional is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT heart [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT heart involvement is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT lung [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT lung involvement is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT skeletal [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT skeletal (joint inflammation and bone density) involvement is assessed on a VAS, 0-100.
  • Myositis Disease Activity Assessment Tool (MDAAT) - MYOACT gasto-intestinal tract. [ Time Frame: 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 skin [ Time Frame: 12 weeks ]
    The MDAAT, MYOACT skin involvement (skin rash) is assessed on a VAS, 0-100.
  • Myositis Damage Index (MDI) - muscle [ Time Frame: 6 months ]
    Degree of skeletal muscle damage is assessed on a VAS, 0-100
  • Myositis Damage Index (MDI) - lung [ Time Frame: 6 months ]
    Degree of lung dagame is assessed on a VAS, 0-100
  • Myositis Damage Index (MDI) gastro-intestinal tract [ Time Frame: 6 months ]
    Degree of GI-tract damage is assessed on a VAS, 0-100.
  • Myositis Damages Index (MDI) Skeletal [ Time Frame: 6 months ]
    Degree of joint damage and osteoporosis is assessed on a VAS, 0-100.
  • Myositis Damage Index (MDI) heart [ Time Frame: 6 months ]
    Degree of damage of the heart is assessed on a VAS, 0-100.
  • Stress echocardiography [ Time Frame: 12 weeks ]
    Systolic heart function is assessed by ultrasound of the heart.
  • Stress echocardiography [ Time Frame: 12 weeks ]
    Diastolic heart function is assessed by ultralsound of the heart
  • Inflammatory infiltrates in skeletal muscle [ Time Frame: 12 weeks ]
    Muscle biopsies are analysed for inflammatory infiltrates with immunohistochemistry.
  • Gene expression [ Time Frame: 12 weeks ]
    Muscle biopsies are analyzed with to Micro Array technique
  • ER-stress [ Time Frame: 12 weeks ]
    Muscle biopies are analysed by ELIZA
  • Proteins involved in kynurenine process [ Time Frame: 12 weeks ]
    Muscle biopsies are analyzed by ELIZA
  • Proteins involved in calcium release [ Time Frame: 12 weeks ]
    Muscle biopsies are analyzed by ELIZA
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of High-intensity Interval Training (HIIT) in Recent Onset Polymyositis and Dermatomyositis
Official Title  ICMJE Effects of High-intensity Interval Training (HIIT) Compared to Low-intensity Exercise in Patients With Recent Onset Polymyositis and Dermatomyositis - a Randomized Controlled Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients are dandomized to either a high-intensity interval group (HIIT) or a control group performing standard low-intensity home exercise.
Masking: Single (Outcomes Assessor)
Masking Description:
The physical therapist performing assessments of muscle function (primary outcome), distributes questionnaires and who is present at maximal oxygen uptake tests and who plan all other assessments logistically is blinded to group allocation. The rheumatologists performing assessment of disease activity and the personell analysing biopsy data are also blinded to group allocation. The care provider is the only one who is not masked.
Primary Purpose: Treatment
Condition  ICMJE
  • Polymyositis
  • Dermatomyositis
Intervention  ICMJE
  • 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.
  • Other: Standard low-intensity home exercise
    12 weeks of 5 days/week low-intensity resistance home exercise in combination with outdoor walks of 20 minutes.
  • Other: 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.
Study Arms  ICMJE
  • Experimental: High-intensity interval training (HIIT) - myositis
    12-week, 3d/w, HIIT
    Intervention: Other: High-intensity interval training (HIIT) - myositis
  • Active Comparator: Standard low-intensity home exercise control (CG)
    12-week, 5 d/w, home exercise.
    Intervention: Other: Standard low-intensity home exercise
  • Active Comparator: High-intensity interval training (HIIT) - healthy
    12-week, 3d/w, HIIT.
    Intervention: Other: High-intensity interval training (HIIT) - healthy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Helene Alexanderson, PhD, Ass.prof +46 8 517745 96 helene.alexanderson@sll.se
Contact: Håkan Westerblad, Professor +46 8 524 872 53 hakan.westerblad@ki.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03324152
Other Study ID Numbers  ICMJE KarolinskaUH1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Muscle biopsies will be sent to Professor Kanneboyina Nagaraju, Professor and Founding Chair, Department of Pharmaceutical sciences, School of Pharmacy and Pharmaceutical Sciences AB-G34, Binghamton University, PO Box 6000 Binghamton, NY 13902-6000. Purpose: To analyse muscle biopsies for micro array analysis.
Supporting Materials: Analytic Code
Time Frame: After completion of the project, muscle biopsies from all patients and healthy subjects will be sent to Dr Nagaraju.
Responsible Party Helene Alexanderson, Karolinska University Hospital
Study Sponsor  ICMJE Karolinska University Hospital
Collaborators  ICMJE Karolinska Institutet
Investigators  ICMJE
Principal Investigator: Helene Alexanderson, PhD, Ass.Prof Karolinska University Hospital and Karolinska Institutet
PRS Account Karolinska University Hospital
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP