AzTrials
AzTrials

COPDCOPD-HIITNCT06068322

Supramaximal High-Intensity Interval Training in People With and Without Chronic Obstructive Pulmonary Disease

A study testing Exercise training on a stationary bicycle in people with COPD and Healthy Controls, run by Umeå University at 2 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Beyond pulmonary complications, COPD presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods. Read more about this study

Who is it for?
Ages 60 years and olderHealthy volunteers can take part
Conditions the study is for
COPD, Healthy Controls
What is being tested?
Exercise training on a stationary bicycle
Could I receive a placebo?
No, everyone receives an active treatment
How many people
208 participants
Where
2 sitesin 2 countries
Study dates
9 Nov 2023to Dec 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

The inclusion criteria are:

  1. 60 years of age or older
  2. Independent in activities of daily living
  3. For people with COPD: Symptomatic (COPD assessment test [CAT] ≥10 or modified Medical Research Council dyspnea scale [mMRC] ≥2) or not being regularly physically active at a moderate or high intensity over the last year defined as not meeting WHO requirements for physical activity.
  4. For people with COPD: Post-bronchodilator spirometry confirmed COPD diagnosis (forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio < 0.70).
  5. For healthy controls: Normal lung function

The exclusion criteria are:

  1. Movement related conditions, cardiovascular, neuromuscular, metabolic, skeletal and/or rheumatic conditions and diseases that are unstable and/or prohibits exercise or tests, based on screening by a physician. For example, but not limited to:
  2. Musculoskeletal pain prohibiting participation in tests and exercise II. Recent myocardial infarction, coronary artery bypass grafting, angioplasty, or other cardiac events III. Uncontrolled arterial hypertension IV. Pathological ECG-findings during CPET
  3. Other lung conditions, including, but not limited to asthma, interstitial lung disease, lung cancer, pulmonary hypertension, pulmonary vascular disease, pulmonary fibrosis
  4. Medical conditions and treatments with known effects on brain function and cognition, for example:
  5. Previous trauma to the head with lasting cognitive or symptom-related issues II. Physical or mental disabilities III. Neurological condition (dementia, multiple sclerosis, stroke) IV. Psychiatric illness, not including depression or general anxiety disorder V. Severe cognitive impairment VI. Recent or current cancer diagnosis and treatment
  6. For those accepting MRI or PET/CT: metal implants, pacemakers, claustrophobia and other MRI incompatible factors.
  7. Inability to read or speak Swedish (Umeå participants), Dutch, French (Hasselt participants) or English (Umeå and Hasselt participants).
  8. For people with COPD:
  9. Co-morbid conditions that limit exercise performance to a greater extent than the COPD diagnosis.

II. Currently participating in a pulmonary rehabilitation program or have been involved in pulmonary rehabilitation in the last 12 months.

III. Experienced a COPD exacerbation that led to a change in medication dosage or frequency in the preceding six weeks.

Trial locations and contacts

2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

André Nyberg, PhD contact

+46 090-786 66 39

andre.nyberg@umu.se

Johan Jakobsson, M.Sc. contact

+46 090 786 63 73

johan.jakobsson@umu.se

2 sites in 2 countries

Belgium1 site, 1 recruiting

  • Hasselt University

    Hasselt, Diepenbeek, 3590

    Jana De Brandt, PhD, 090-786 63 73 ext. +46, jana.de.brandt@umu.se

    Chris Burtin, PhD

    Recruiting

Other trials in Belgium

Sweden1 site, 1 recruiting

  • Umeå University

    Umeå

    Andre Nyberg, PhD, andre.nyberg@umu.se

    Andre Nyberg, PhD

    Recruiting

Other trials in Sweden

About this study

Official title: Effects and Mechanisms of Supramaximal High-Intensity Interval Training in People With and Without Chronic Obstructive Pulmonary Disease on Extrapulmonary Manifestations

Beyond pulmonary complications, COPD presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods.

The COPD-HIIT trial intend to investigate the effects and mechanisms of 12 weeks supramaximal high-intensity interval-training (HIIT) compared to moderate intensive continous training (MICT) in people with COPD and matched healthy controls on important clinical outcomes.

The trial also intends to compare the effects of 24 months of exercise training (supramaximal HIIT or MICT) to usual care in people with COPD on brain health, cardiorespiratory fitness and muscle power; in people with COPD.

Read the detailed description

COPD-HIIT is a prospective, multi-centre, randomised, controlled, parallel-group superiority trial with assessor and data analyst blinding, featuring a 1:1 allocation ratio and two separate phases. In Phase 1, the trial will investigate the effects and mechanisms of a 12 week intervention with supramaximal HIIT compared to MICT in people with COPD and matched healthy controls. Upon completing the initial 12 week intervention and follow-up assessments, people with COPD, but not healthy controls, will enter Phase 2 of the trial. Phase 2 comprises a 21 month maintenance exercise program. Subsequently, exercise training (supramaximal HIIT or MICT) will be performed until a 24 month follow-up. A separate control group of people with COPD, receiving usual care only, will undergo assessments at baseline and 24-months, making Phase 2 a partially randomized controlled trial.

The primary objectives are:

  1. to determine and compare the effect of 12-weeks of supramaximal HIIT and MICT on cognitive function, cardiorespiratory fitness, and muscle power in people with COPD compared to matched healthy controls (Phase 1).
  2. to determine and compare the effect of 24-months of supramaximal HIIT, MICT and usual care on cognitive function, cardiorespiratory fitness and muscle power in people with COPD (Phase 2).

Phase 1 and 2 of the COPD-HIIT project will be performed at two recruiting centres. 1) Department of Community Medicine and Rehabilitation, Physiotherapy, Umeå University, Umeå, Sweden and Norrlands Universitetssjukhus, and 2) Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium and Ziekenhuis Oost-Limburg (ZOL, Genk, Belgium).

In Phase 1, eligible participants will be randomized to either supramaximal HIIT (intervention arm) or MICT (active control arm) on a stationary bicycle (Smart ZBike, Zycle, Valencia, Spain). For both arms, training is performed two to three times per week for a total of 30 sessions (Table 1) using a group format with groups of 4-8 participants at the same time. Both protocols enable controlled and systematic adjustments of training intensity by means of standardized criteria to achieve a progressive overload

Regarding supramaximal HIIT, importantly, while the intensity is supramaximal, it is dosed and performed at a given fraction of the maximum capacity that the person can produce during the bout (6-seconds). In contrast to an all-out regimen, or sprint interval training (SIT), this allows for the introduction and titration of intensity to the highest acceptable level without the individual feeling unwell during the process.

In Phase 2, participants with COPD will enter a 21 month maintenance phase. They will continue to exercise using the same training modality (HIIT or MICT) as during the first 12-weeks but can select between three different settings to continue their training: "Home", "Outpatient", or "Mix" setting. Notably, the participant can, at any time during the maintenance period, change between the "Home", "Outpatient" or "Mix" settings when conducting their endurance training. Irrespective of the originally assigned group (supramaximal HIIT or MICT) or if the participant selects to continue in "Home", "Outpatient" or "Mix" setting, they will also perform a resistance training (RT) regime. The RT regime will consist of ten lower and upper-body exercises designed following American College of Sports Medicine guidelines and other relevant RT literature for increasing muscular strength, endurance, and power.

All exercise sessions will be held and supervised by an experienced health care professional, such as physiotherapists, exercise physiologists or other health professional with equivalent expertise. All intervention providers will receive training on exercise intervention protocols to ensure standardization among centres.

The between-group effects will be analyzed using analysis of covariance (ANCOVA). In the ANCOVA, baseline values, age, sex, center and VO2peak will be used as covariates. There will be one model for the COPD group and one for HC. To investigate any differential effects to the interventions between COPD and HC, an additional model including the Group (COPD/HC) × Intervention (HIIT/MICT) will be performed. Furthermore, pre-specified longitudinal mediation analyses will be performed on the entire MRI and PET/CT sample between changes in VO2peak, neurodegenerative measures, e.g., cognitive function and hippocampal volume, and inflammation levels between baseline and 24 months.

Analyses will employ the intention-to-treat when applicable. Meaning that all participants randomized, whether they receive their allocated intervention or withdrew from the trial, will be included in the analysis. The primary analyses are performed using Multiple Imputation by Chained Equations (MICE) for missing data. The imputation will be done separately for each intervention arm. In addition, a per-protocol analysis (defined as > 75% attendance rate as well as no exacerbations during the last two weeks prior to follow-up assessment), and a complete-case analysis (including participants with complete outcome measurements independent on attendance rate) will be reported.

The full study protocol adheres to the SPIRIT guidelines and its outcomes extension, with intervention descriptions further guided by the TIDieR checklist the Consensus on Exercise Reporting Template (CERT). Publications from COPD-HIIT will follow the CONSORT statement, or relevant guidelines at the time of publication. Publications including qualitative outcomes will also be guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ).

Being tested
Exercise training on a stationary bicycle
Keywords
Chronic obstructive Pulmonary Disease, Pulmonary Disease, Chronic Obstructive, Chronic airway disease, COPD, physical activity, exercise
Medical subject headings
Pulmonary Disease, Chronic Obstructive, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Exercise training on a stationary bicycleOther

    Training is performed two to three times per week for a total of 30 sessions using a group format.

    Both regimens start with a five-minute warm-up and ends with a five-minute cool-down, performed at an intensity corresponding to 30% of the maximal work rate achieved during a CPET (i.e., max aerobic power [MAP]) with a self-selected pedalling cadence of 50-70 revolutions per minute (RPM).

    All exercise sessions will be held and supervised by an experienced health care professional, i.e. physiotherapists or other health professional.

    The different types of exercise training is described under the specific arm.

    Following the first 12-week training period, participants with COPD will enter a 21-month maintenance phase. They will continue to exercise using the same training modality (HIIT or MICT) as during the first 12-weeks but can select between three different settings to continue their training: "Home", "Outpatient", or "Mix" setting.

Study groups in NCT06068322
Study groupRoleWhat they receive
Supramaximal high-intensity interval training (Supramaximal HIIT)ExperimentalEach HIIT session consists of 10 repeated 6-seconds regulated high intensity cycling sprints against an individualized load set to reach a supramaximal exercise intensity (i.e. power output is higher than power output at maximum oxygen uptake). Session duration for HIIT is initially 20 min, including warm-up (5 min) and cool-down (5 min). The protocol enables controlled and systematic adjustments of training intensity by means of standardized criteria.
Receives: Other: Exercise training on a stationary bicycle
Moderate-intensity continuous training (MICT)Active comparatorEach MICT session will consist of aerobic training regulated against an individualized load set to reach a moderate submaximal exercise intensity (i.e. power output is lower than power output at maximum oxygen uptake). Session duration for MICT is initially 30 min, including warm-up (5 min) and cool-down (5 min). The protocol enables controlled and systematic adjustments of training intensity by means of standardized criteria.
Receives: Other: Exercise training on a stationary bicycle
Usual careNo interventionThe passive control group will receive usual care alone and a standardized phone call every three months including assessments of health status (CAT), disease specific quality of life (CRQ) and questions on symptoms of exacerbations. We will match the participants in the standard care group to those randomized to HIIT or MICT by age, sex, disease severity, educational level, and physical activity.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline global cognitive function

    Global cognitive function will be assessed as the Z-score determined by the combined performances on six tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the trail making test (TMT-A, TMT-B). The following tests from the CANTAB will be used: Motor screening task, reaction time, visual information processing, paired associates learning, spatial working memory, verbal recognition memory. The test battery takes around 60 minutes to complete. The test scores from the seven tests will be combined into a composite Z-score. The Z-score describes how much a point deviates from a mean or specific point. The Z-score represents how many standard deviations an individual's score is from the mean score of the reference population, which is represented as zero.

    Measured: Baseline, 12 weeks, 24 months

  2. Change from baseline cardiorespiratory fitness

    Measured as maximum oxygen uptake (VO2peak [ml O2/min/kg]) during a standardized ramp-protocol cardiopulmonary exercise test (CPET) on a cycle ergometer. The CPET will start with a 3-minute resting phase before a 3-minute unloaded (or lowest wattage possible) warm-up phase. The aim is to have a ramp-phase of 8-12 minutes, until the participant stops due to voluntarily exhaustion, symptom-limitation or failure to maintain a cadence of 50-70 RPM.

    Measured: Baseline, 12 weeks, 24 months

  3. Change from baseline quadriceps muscle power

    Peak power (Nm/s) assessed during a seated leg extension in a dymanometer (Biodex System 4). Participants will be instructed to extend their leg as fast and as hard as possible and then passively return the leg to the starting position.

    Measured: Baseline, 12 weeks, 24 months

Secondary outcomes (64)

  1. Change from baseline brain structure

    Assessed using standard MRI-sequences including in a 3 Tesla MRI-scanner. T1-weighted images will be used to determine volumes of grey matter, white matter and lateral ventricle size. T2-weighted, fluid-attenuated inversion recovery (FLAIR), and susceptibility weighted (SW) images are collected to assess perivascular spaces, lacunes, white-matter lesions and microbleeds. For structural MRI data volume (mm3), area (mm2) and cortical thickness (mm) will be the unit of measure.

    Measured: Baseline, 12 weeks, 24 months

  2. Change from baseline brain activity

    Task-based functional MRI will be performed to evaluate brain activity in the hippocampus and prefrontal cortex, measured as BOLD signal change.The face-name association task will be used.

    Measured: Baseline, 12 weeks, 24 months

  3. Change from baseline cerebral perfusion

    Assessed using arterial spin labelling (ASL) in a 3T MRI-scanner (mL/100g/minute).

    Measured: Baseline, 12 weeks, 24 months

  4. Change from baseline neuroinflammation

    In vivo neuroinflammation is measured as uptake rate (ki) of 11C-deprenyl in the brain assessed with PET/CT (General Electric, WI, USA) under resting-state conditions after intravenous injection of 314 MBq of 11C-Deprenyl. . Uptake rate of 11C-deprenyl in the brain is modeled with Patlak analyses, where higher uptake is representative of higher levels of inflammation.

    Measured: Baseline, 12 weeks, 24 months

  5. Change from baseline exercise tolerance

    Test duration (mm:ss) on a constant-workload cycle test (CWRT) set at 75% of maximal power achieved during a CPET. After a 3-minute resting phase and a 3-minute warm-up phase at 30% of MAP, participants will cycle at a constant workload corresponding to 75% of MAP with a self-selected pedaling cadence of 50-70 RPM. Participants will be instructed to exercise for as long as possible.

    Measured: Baseline, 12 weeks, 24 months

  6. Change from cardiorespiratory fitness

    A intermediate test at 6-weeks will be done to regulate training intensity and the result will be used as a secondary outcome. Measured as maximum oxygen uptake (VO2peak [ml O2/min/kg]) during a standardized ramp-protocol cardiopulmonary exercise test (CPET) on a cycle ergometer. The CPET will start with a 3-minute resting phase before a 3-minute unloaded (or lowest wattage possible) warm-up phase. The aim is to have a ramp-phase of 8-12 minutes, until the participant stops due to voluntarily exhaustion, symptom-limitation or failure to maintain a cadence of 50-70 RPM.

    Measured: Baseline, 6 weeks

  7. Change from baseline lactate concentration during constant-workload cycle test (CWRT)

    Capillary blood lactate (mmol/L) will be measured during and immediately after the CWRT to assess the metabolic demand.

    Measured: Baseline, 6 weeks, 12 weeks, 24 months

  8. Change from baseline cognitive function: Motor screening task

    Test score in the CANTAB Motor screen task. During the test, colored crosses appear in different locations on the screen. The participant must select the cross as quickly and accurately as possible.

    Measured: Baseline, 12 weeks, 24 months

  9. Change from baseline cognitive function: Reaction time

    Test score in the CANTAB reaction time test. During the test, participants must select a button on the screen. Circles are presented above the button and the participant is asked to react as soon as possible once a yellow dot appears in one of the circles by clicking the corresponding circle.

    Measured: Baseline, 12 weeks, 24 months

  10. Change from baseline cognitive function: Visual information processing

    Test score in the CANTAB Visual information processing test. During the test, a white box is shown in the center of the screen where digits from 2 to 9 appear in a pseudo-random order at the rate of 100 digits per minute. Participants are requested to detect target sequences of digits (e.g., 2-4-6, 3-5-7, 4-6-8). When the participant sees the target sequence, they must respond by selecting the button in the center of the screen as quickly as possible.

    Measured: Baseline, 12 weeks, 24 months

  11. Change from baseline cognitive function: Paired associates learning

    Test score in the CANTAB Paired associates learning test. In the test, boxes are displayed on the screen and are opened in a randomized order. One or more of them will contain a pattern. The patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located.

    Measured: Baseline, 12 weeks, 24 months

  12. Change from baseline cognitive function: Spatial working memory

    Test score in the CANTAB spatial working memory test. During the test, several colored boxes are shown on the screen. The aim of this test is that, by selecting the boxes and using a process of elimination, the participant should find one yellow 'token' in each of several boxes and use them to fill up an empty column on the right-hand side of the screen

    Measured: Baseline, 12 weeks, 24 months

  13. Change from baseline cognitive function: Executive function

    Test score in the trail making test. The TMT consists of two parts, A and B and is performed with paper and pencil. During part A, the participant needs to connect 25 digits in ascending order as fast as possible by drawing lines between the digits. During part B, the participants need to connect 13 digits in ascending order and 12 letters in alphabetical order, alternating digits, and letters (i.e., 1 - A - 2 - B - 3 - C, etcetera) as fast as possible by drawing lines between the digits and letters.

    Measured: Baseline, 12 weeks, 24 months

  14. Change from baseline anaerobic exercise capacity

    Intensity (produced power, in watts) at the final stage during a Borg cycle strength test (BCST). The BCST is a submaximal cycle ergometer test that is used to estimate maximum mean power output for 30 seconds (MPO30) without an all-out effort. The BCST consists of 30-second efforts with increasing intensity, interspersed with 30-seconds passive recovery between each effort. With a target pedaling cadence of 80-90 RPM, participants cycle until they score an RPE of ≥17, or when they cannot keep the target cadence (<75 RPM for five seconds).

    Measured: Baseline, 12 weeks, 24 months

  15. Change from baseline cognitive function: Verbal recognition memory

    Test score in the CANTAB verbal recognition memory test. During the test, the participant is shown a list of words to remember. During the recognition phase, the participant is asked to say whether they remember seeing the word on the screen before. The word can be one of the originals, or a new word (distractor) which they have not yet seen before.

    Measured: Baseline, 12 weeks, 24 months

  16. Change from baseline chronic inflammation

    Levels of hs-CRP in venous blood. Unit of measure is mg/L.

    Measured: Baseline, 12 weeks, 24 months

  17. Change from baseline inflammatory markers

    Llevels of interleukin-6, interleukin-8 and TNF-alpha in venous blood. Unit of measure is pq/mL.

    Measured: Baseline, 12 weeks, 24 months

  18. Change from baseline fibrinogen

    Plasma levels of fibrinogen. Unit of measure is g/L.

    Measured: Baseline, 12 weeks, 24 months

  19. Change from baseline blood cell count

    White blood cells and eosinophils measured in whole blood. Unit of measure is count x 10^9/L.

    Measured: Baseline, 12 weeks, 24 months

  20. Change from baseline neurotrophic factors

    Levels of BDNF, irisin, IGF-1, Cathepsin B and clusterin in venous blood samples. Unit of measure is pq/ml.

    Measured: Baseline, 12 weeks, 24 months

  21. Change from baseline resting lactate

    Concentration of lactate in capillary blood samples. Unit of measure is mmol/L.

    Measured: Baseline, 12 weeks, 24 months

  22. Change from baseline blood lipid profile

    Total cholesterol, LDL, HDL, non-HDL and triglycerides. Unit of measure is mmol/L.

    Measured: Baseline, 12 weeks, 24-months

  23. Change from baseline metabolic function: Glucose

    Plasma levels of glucose in fasted venous blood sample. Unit of measure is mmol/L.

    Measured: Baseline, 12 weeks, 24-months

  24. Change from baseline metabolic function: Insulin

    Plasma levels of insulin in fasted venous blood sample. Unit of measure is mIU/L.

    Measured: Baseline, 12 weeks, 24-months

  25. Change from baseline metabolic function: Insulin resistance

    Levels of glucose and insulin levels will be used to calculate the HOMA-IR (Homeostatic Model Assessment of Insulin Resistance). The unit of measure is arbitrary units where values above 1.9 indicates early insulin resistance, and above 2.9 indicates significant insulin resistance.

    Measured: Baseline, 12 weeks, 24-months

  26. Change from baseline metabolic function: Glycated hemoglobin

    Levels of Hb1Ac, measured as a percentage (%) of red blood cells that is bound to glucose.

    Measured: Baseline, 12 weeks, 24-months

  27. Change from baseline quadriceps muscle strength

    Muscle strength will be determined as the one-repetition maximum (1-RM) defined as the maximum torque (Nm/s) able to be lifted through the full range of motion during seated leg extension in the dominant leg, using a dymanometer (Biodex System 4)

    Measured: Baseline, 12 weeks, 24 months

  28. Change from baseline quadriceps muscle endurance

    Defined as the maximum number of repetitions able to be lifted with a good technique through the full ROM at an intensity corresponding to 45% of 1-RM, during seated leg extension in the dominant leg, using a dymanometer (Biodex System 4).

    Measured: Baseline, 12 weeks, 24 months

  29. Change from baseline functional performance: Five time sit-to-stand test (5-STS)

    Time needed (in seconds) to complete the 5-STS.

    Measured: Baseline, 12 weeks, 24 months

  30. Change from baseline functional performance: Stair climbing power test

    Time needed (in seconds) to ascent a 10-step flight of stairs.

    Measured: Baseline, 12 weeks, 24 months

  31. Change from baseline muscle fibre size

    The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analyses to determine cross-sectional fiber area of all fibres and per subtype. Unit of measurement is square micrometers.

    Measured: Baseline, 12 weeks

  32. Change from baseline proportion of slow and fast subtypes of contractile myosin heavy chain isoforms

    The tissue sample obtained from the vastus lateralis muscle will be examined with immunohistochemistry techniques to categorize fiber types. Expressed as relative distribution in percent and relative area of the muscle in percent.

    Measured: Baseline, 12 weeks

  33. Change from baseline capillary density

    The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analysis to determine capillary density, estimated as the total number of capillaries per millimeter squared muscle cross-section.

    Measured: Baseline, 12 weeks

  34. Change from baseline capillaries per fiber

    The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analysis to determine the number of capillaries in close contact with each muscle fiber. Unit of measure is number of capillaries in close contact with fibre.

    Measured: Baseline, 12 weeks

  35. Change from baseline capillaries to fiber area

    The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analysis to determine the number of capillaries around each fiber relative to its cross-sectional area.

    Measured: Baseline, 12 weeks

  36. Change from baseline capillaries sharing factor

    The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analysis to determine the capillary-to-fiber ratio

    Measured: Baseline, 12 weeks

  37. Change from baseline myofiber and mitochondrial disruption/abnormalities (NADH-TR)

    Staining of reduced nicotinamide adenine dinucleotide-tetrazolium reductase, succinate dehydrogenase, and cytochrome c oxidase. Measured as % of fibers with abnormal staining pattern and fiber area in µm2 of fibers with abnormal staining pattern.

    Measured: Baseline, 12 weeks

  38. Change from baseline mitochondrial biogenesis

    mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) alpha and PGC-1beta. Unit of measure is fold-change or arbitrary units.

    Measured: Baseline, 12 weeks

  39. Change from baseline enzyme activity

    Enzyme activities of phosphofructokinase (PFK; glycolysis), lactate dehydrogenase (LDH; anaerobic glycolysis), citrate synthase (CSM Krebs cycle), succinate dehydrogenase (SDH; Krebs cycle), 3-hydroxyacyl Coenzyme A dehydrogenase (HADH; beta-oxidation) and mitochondrial complex I-V. Unit of measure is micromol/min/g tissue.

    Measured: Baseline, 12 weeks

  40. Change from baseline enzyme content

    Enzyme content of phosphofructokinase (PFK; glycolysis), lactate dehydrogenase (LDH; anaerobic glycolysis), citrate synthase (CS; Krebs cycle), succinate dehydrogenase (SDH; Krebs cycle), 3-hydroxyacyl Coenzyme A dehydrogenase (HADH; beta-oxidation) and mitochondrial complex I-V. Unit of measure is micromol/min/g tissue.

    Measured: Baseline, 12 weeks

  41. Change from baseline angiogenesis

    mRNA and protein level of VEGF (fold change or arbitrary units).

    Measured: Baseline, 12 weeks

  42. Change from baseline proteins related to muscle-brain cross talk

    mRNA and protein level of BDNF, fibronectin type III domain-containing protein 5 (FNDC5) and kynurenine aminotransferase (KAT1-4). Unit of measure is fold change and arbitrary units.

    Measured: Baseline, 12 weeks

  43. Change from baseline modulation of autonomic cardic function

    Resting heart rate variability measured in the time domain as the root mean square of the successive differences (RMSSD, in milliseconds), and time domain (LH:HF ratio) using a chest strap heart rate monitor.

    Measured: Baseline, 12 weeks, 24 months

  44. Change from baseline blood pressure

    Resting blood pressure, measured as systolic and diastolic pressure in mmHg.

    Measured: Baseline, 12 weeks, 24 months

  45. Change from baseline epigenetic modifications in muscle samples

    Samples will be analysed for genome-wide DNA methylation, via the EPICarray technology.

    Measured: Baseline, 12 weeks

  46. Change from baseline epigenetic modifications in blood samples

    Whole blood EDTA samples will be analysed for genome-wide DNA methylation, via the EPICarray technology.

    Measured: Baseline, 12 weeks, 24 months

  47. Change from baseline body composition

    Body composition measures include body mass index, waist and hip circumference (cm), percentage of body fat, fat-free mass (kg), and fat-free mass index (kg/m2). Fatmass and fatfree mass is measured with bioelectrical impedance.

    Measured: Baseline, 12 weeks, 24 months

  48. Change from baseline impact of COPD in daily life

    Measured vid the COPD Assessment Test (CAT)

    Measured: Baseline, 12 weeks, 6 months, 12 months, 15 months, 18 months, 21 months and 24 months

  49. Change from baseline disease specific quality of life

    Measured with the chronic respiratory disease questionnaire (COPD group only). The CRQ measures the impact of chronic respiratory disease on HRQoL and covers four key domains of HRQoL, including: dyspnea, fatigue, emotional function, and mastery. Each item is scored on a 7-point Likert scale; scores within each domain are summated for a total score per domain.

    Measured: Baseline, 12 weeks, 6 months, 12 months, 15 months, 18 months, 21 months and 24 months

  50. Change from baseline Health related quality of life

    Measured with the EQ-5D-5L questionnaire.It assesses an individual's HRQoL in five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression91. Each dimension has five response levels, ranging from level 1 (no problems) to level 5 (extreme problems). By combining one level from each dimension, a health state ranging from 11111 (the best health state) to 55555 (the worst health state) is defined and converted into an index score using a scoring algorithm.

    Measured: Baseline, 12 weeks, 24 months

  51. Change from baseline state of depression and anxiety

    The Hospital Anxiety and Depression Scale (HADS) will be used to assess states of depression and anxiety. The HADS is a reliable 14-item questionnaire regarding feeling of depression and anxiety in the past week which can be answered within 2 - 5 minutes. A separate score is given for depression and anxiety. where a higher score means higher severity.

    Measured: Baseline, 12 weeks, 24 months

  52. Self-percieved change

    Self-perceived change in outcomes will be measured via the Global Rate of Change scale with the purpose to quantify the extent to which a participant's outcomes have improved or deteriorated over time. Participants will provide an answer via a 11-point Likert scale (-5 = "Much worse"; 0 = "Unchanged"; 5 = "Much better").

    Measured: 12 weeks, 24-months

  53. Number of responders

    Total amount of responders, defined as a response over the known minimal detectable change or minimal important difference for included tests, will be determined, and compared between HIIT and MICT.

    Measured: 12 weeks, 24-months

  54. Feasibility of interventions: Completion rate

    Completion rate is determined by the total number of participants still performing the exercise training intervention at 12-week and 24-month follow-up. Reasons for non-completion are also obtained.

    Measured: 12-weeks and 24-months

  55. Feasibility of interventions: Attendance rate

    Attendance rate is determined by the total number of attended sessions divided by total number of sessions prescribed, presented as a percentage. Reasons for non-attendance are also obtained.

    Measured: 12-weeks and 24-months

  56. Feasibility of interventions: Exercise fidelity

    Exercise fidelity is determined as the incidence of exercise sessions requiring modifications, defined as any deviation from the prescribed exercise.

    Measured: Throughout the whole intervention period (24-months)

  57. Feasibility of interventions: Adherence to exercise duration and intensity

    Adherence to exercise duration is determined as the adherence to the predefined intervals/minutes of the exercise training. Reasons for non-adherence are also obtained. Adherence to exercise intensity is determined as the adherence to the prescribed intensity of the exercise training. Reasons for non-adherence are also obtained. Exercise intensity (absolute workload [W], relative intensity [% of MAP, % of MPO6], the level of dyspnoea and leg fatigue [0-10, arbitrary units] on the Borg CR10 scale and perceived exertion [6-20, arbitrary units] on the Borg Rating of RPE scale.

    Measured: Throughout the whole intervention period (24-months)

  58. Feasibility of interventions: Satisfaction

    Participant satisfaction with the performed exercise training (supramaximal HIIT / MICT) will be recorded by adaptation of an existing patient satisfaction questionnaire previously used cycling exercises in COPD. (Evans et. al. Ann Am Thorac Soc 2015)

    Measured: Throughout the whole intervention period (24-months)

  59. Feasibility of interventions: Affective responses

    Affective response/mood will be measured using the Feeling scale, during and after exercise sessions. The Feeling scale ranges from -5 to +5, where a higher score indicates a better feeling.

    Measured: Throughout the whole intervention period (24-months)

  60. Adverse events

    Adverse events are rated into four different categories: 1) minor and temporary, 2) serious symptoms (potential risk of severe injury or life threatening, 3) manifest injury or disease, and 4) death, as previously described. An adverse event rate will be calculated for each participant as the total number of sessions during which any adverse events occurred divided by the total number of attended sessions.

    Measured: Throughout the whole intervention period (24-months)

  61. Experiences of exercising and its effects

    Face-to-face interviews will explore the participants' experiences and perceptions of participating in the program.

    Measured: 12 weeks, 24-months

  62. Hospitalisations

    Number of hospitalisations per participant during the study period. Time, cause, length of stay, and emergency room visits (with no hospitalization afterwards) and their cause will also be extracted. Hospitalizations and emergency room visits will be classified as respiratory or non-respiratory. In Phase 2, data on hospitalizations will be extracted from the participant's medical record and cross-checked with the participant's diary.

    Measured: 24 months

  63. Mortality

    Number of deaths during the study period will be extracted from the participant's medical record. Time and cause of each death will also be extracted.

    Measured: 24 months

  64. Exacerbations

    In the COPD groups, number of exacerbations during the whole study period will be recorded during the whole study period. In Phase 2, data on exacerbations will be extracted from the participant's medical record and cross-checked with the participant's diary.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2023
  2. Study start9 Nov 2023
  3. Primary completionDec 2028 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
In Phase 1, participants will be randomised to either interventional arm or control arm with a 1:1 allocation ratio, using a computer-generated block randomisation schedule stratified for sex (male, female), age and centre with equal allocation to all study arms. For Phase 2 only the participants with COPD will continue the maintenance program in their allocated group. A usual of care group consisting of patients with COPD will also be recruited to serve as control in the maintenance part.
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
208 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06068322
Sponsor's protocol ID
COPD-HIIT RCT
Other IDs
2020-01296, 2020-0139, 101078602
Acronym
COPD-HIIT
Status last verified
May 2024
First submitted
26 Jun 2023
Last updated
23 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: We strive to share all the IPD that underlie results in a publication in a open data repository, if this will be possible given regulations and agreements at that time.

Publications

  • Jakobsson J, Burtin C, Hedlund M, Boraxbekk CJ, Westman J, Karalija N, Stal P, Sandstrom T, Ruttens D, Gosker HR, De Brandt J, Nyberg A. Effects and mechanisms of supramaximal high-intensity interval training on extrapulmonary manifestations in people with and without chronic obstructive pulmonary disease (COPD-HIIT): study protocol for a multi-centre, randomized controlled trial. Trials. 2024 Oct 8;25(1):664. doi: 10.1186/s13063-024-08481-3.

    PubMed 39375781

Questions about this trial

What is this clinical trial studying?

A study testing Exercise training on a stationary bicycle in people with COPD and Healthy Controls, run by Umeå University at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Belgium, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact André Nyberg, PhD (+46 090-786 66 39, andre.nyberg@umu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline global cognitive function (time frame: Baseline, 12 weeks, 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06068322, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.

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