COPDNCT07707271
Continuous Versus High Intensity Interval Exercise in Chronic Obstructive Pulmonary Disease
A study testing Moderate intensity continuous aerobic exercise (MICE) and High-intensity interval aerobic exercise (HIIE) in people with COPD, run by George Papanicolaou Hospital at 1 site in Greece.
Trial summary
Chronic Obstructive Pulmonary Disease (COPD) is characterized by exercise intolerance, which is a prognostic factor of disease severity and mortality and is usually attributed to ventilatory limitations. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- COPD
- What is being tested?
- Moderate intensity continuous aerobic exercise (MICE) and High-intensity interval aerobic exercise (HIIE)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteGreece
- Study dates
- 15 Jun 2026to Jul 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical diagnosis of COPD based on smoking history (pack/years) or exposure to other risk factors and post bronchodilation forced expiratory volume (FEV1) to forced vital capacity (FVC) ratio <0.7
- Resting arterial oxygen partial pressure at room air >60 mmHg, according to recent (within a week) arterial blood gases assessment
- Disease being stable and treated optimal, based on current GOLD guidelines.
- Provision of informed written signed consent prior to study entry
Who cannot join
- Recent respiratory infection or exacerbation (as indicated by deterioration of respiratory symptoms, hospital admission and/or change in medication within the previous month), within the past 3 months
- Changes in COPD medication with the past month
- History of asthma and/or reversible airway obstruction (post bronchodilation FEV1/ FVC >0.7)
- Pulmonary hypertension
- Congestive heart failure (Left Ventricle Ejection Fraction <50% in recent echocardiography)
- Severe peripheral artery disease
Show all 12Show fewer
- Chronic Kidney disease with eGFR < 30 ml/min (KDIGO stages 3b, 4 ,5)
- Active acute or chronic infectious diseases
- Active malignant disease or hematologic disorder under treatment
- History of neuromuscular disorder
- History of severe intellectual disability or mental disorder
- Any contradiction to moderate-high intensity exercise or cardiopulmonary exercise testing according to ATS/ACCP guidelines, such as: myocardial infarction within the past 6 months, unstable angina, syncope, symptomatic severe aortic stenosis, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute pulmonary embolus or pulmonary infarction, thrombosis of lower extremities, suspected dissecting aneurysm, pulmonary edema, severe untreated arterial hypertension at rest (> 200 mm Hg systolic, > 120 mm Hg diastolic blood pressure), orthopedic impairment that compromises exercise performance.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Greece1 site, 1 recruiting
- Recruiting
George Papanikolaou General Hoapital of Thessaloniki
Thessaloniki, Exohi, 57010
Afroditi Boutou, 00306946611433, afboutou@yahoo.com
Aikaterini Gakidi
About this study
Official title: Changes in Brain Oxygenation, Cadiopulmonary Parameters and Autonomic Nervous System Function During Moderate Intensity Continuous Versus High Intensity Interval Exercise in Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease (COPD) is characterized by exercise intolerance, which is a prognostic factor of disease severity and mortality and is usually attributed to ventilatory limitations. Emerging evidence indicates that cerebral oxygenation may also be an important contributor, being impaired both at rest and during exercise in COPD patients. Furthermore, abnormal systemic hemodynamic responses and autonomic nervous system (ANS) dysfunction have been observed, which may further impair cerebral oxygenation. The type of exercise training applied in pulmonary rehabilitation (continuous versus interval) appears to influence these mechanisms differently, yet evidence on their impact on cerebral oxygenation in COPD remains scarce. The aim of this study is to compare, for the first time, the acute changes in cerebral oxygenation, CPET parameters, systemic hemodynamic responses, and autonomic responses in patients with COPD who undergo a high-intensity interval aerobic exercise (HIIE) protocol versus a moderate-intensity continuous aerobic exercise (MICE) protocol. These findings will have important clinical implications, as they may guide the choice of the most appropriate exercise modality in pulmonary rehabilitation.
Read the detailed description
This is a single-centre, prospective, randomized, cross-over clinical trial that will be conducted at "G. Papanikolaou Hospital, Thessaloniki, Greece. For the purposes of this study, COPD patients that fulfil the inclusion/exclusion criteria will be recruited from Pulmonary Outpatient Clinics of "G. Papanikolaou" General Hospital of Thessaloniki and included after signing a written informed consent form. The study protocol was approved by the Ethics Committee of the School of Medicine, Aristotle University of Thessaloniki. All procedures and evaluations will be performed according to the Declaration of Helsinki 2013 Amendment.
The study will be conducted in a total of 4 visits including baseline assessment. At baseline assessment (visit 1), all subjects will provide a detailed medical history including smoking history, comorbidities, history of acute COPD exacerbations and severity of dyspnea (based on the modified Medical Research Council dyspnea scale). Then, they will undergo a post-bronchodilation spirometry, assessment of diffusion capacity (DLCO), measurement of lung volumes and blood pressure measurements after 10min of rest. Arterial blood gases sampling (breathing room air) will be collected, to confirm lack of resting hypoxemia. Moreover, data regarding physical activity will be collected, using the short form of International Physical Activity Questionnaire (IPAQ). The eligible patients that will be recruited will be advised to refrain from food for 4h and from caffeine, alcohol, or tobacco for 12 h and receive any standard medication before their morning appointment in the research laboratory to perform the assessments described below.
Visit 2 will be conducted with a week of baseline visit. and visits 3 and 4 will take place at least 72h after visit 2. During visit 2, all recruited patients will undergo a cardiopulmonary exercise test (CPET) on a cycle ergometer using an incremental exercise RAMP protocol to exhaustion to establish peak work rate (WRpeak). For visits 3 and 4, all patients will perform in random order on different visits (separated by one week) two exercise protocols on the same cycle ergometer, a high-intensity interval aerobic exercise (HIIE) protocol and a moderate-intensity continuous aerobic exercise (MICE) protocol. The HIIE protocol will consist of 60 seconds work at 85% WRpeak followed by 60 seconds of rest and the MICE protocol will include 20 minutes of cycling at 50% WRpeak. Exercise protocols will be matched for total workload. All parameters will be recorded at rest (3 minutes), during unloaded warm-up (3 minutes), during the exercise and during 3-min recovery following the completion of exercise bouts. The rate of perceived exertion (1-10 Borg scale), legs' perceived exertion (1-10 Borg scale), dyspnea (0-10 scale), and will be assessed every 3 min and at exercise termination.
During the CPET and the protocols, respiratory gas exchange will be recorded using a metabolic cart (Ultima CPX™, MGC Diagnostics). Breath-by-breath values for minute ventilation (VE), respiratory rate (RR), tidal volume (Vt), oxygen uptake (VO2), and end-expiratory pressure of carbon dioxide (PETCO2) will be recorded, along with derived variables. Maximum Minute Ventilation (MVV) will be calculated using the formula "Forced Expiratory Volume in 1 s (FEV1) x 40". A 12-lead electrocardiogram and oxygen saturation (SpO2, finger pulse oximetry) will be continuously monitored.
For cerebral oxygenation assessment, near-infrared spectroscopy (NIRS, OxyMon, Artinis Medical Systems, Elst, the Netherlands) will continuously monitor, non-invasively, changes in cerebral oxygenation, by measuring the micromolar (μΜ) relative changes from (resting conditions for oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), total hemoglobin (tHb), and Hb-difference. The NIRS probes will be placed over the patients' left prefrontal lobe between Fp1 and F3, according to the modified international EEG 10-20 system, with the receiving sensor fixed laterally to the emitter at a distance of 4.5 cm.
Hemodynamic parameters will be continuously and non-invasively assed using a photoplethysmography apparatus (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands) connected to the participants' finger. This device allows beat-to-beat tracing of systolic and diastolic blood pressure (SBP and DBP relatively, mmHg), mean arterial pressure (MAO, mmHg) and heart rate (HR). Beat-by-beat HR and stroke volume (SV, ml) will be computed using the Modelflow method, an arterial pressure wave analysis which has been shown to be a reliable alternative to invasive thermodilution techniques at rest and during exercise. Cardiac output (CO, L/min), systemic vascular resistance (SVR, mmHg.s/mL) and ejection time (EJT, s) will be estimated using the BeatScope software (Beatscope version 1a, Finometer, Finapres Medical Systems). Autonomic responses will be assessed using the non-linear components of Heart Rate Variability (HRV) with Kubios software (Kubios, version 3.3.1, Kubios Oy, 2019). The root mean square of successive differences (RMSSD), an index of parasympathetic system activity, will be calculated. The standard deviation perpendicular to the line-of-identity SD1 (an index of parasympathetic system activity), the standard deviation along the line-of-identity (SD2) and their ratio (SD1/SD2) (an index of vagal/sympathetic function) will be analysed, since these measures are not affected by changes in respiration patterns. Baroreflex sensitivity (BRS, ms/mmHg) will be assessed by examining the spontaneous fluctuations in the blood pressure as assessed by a cross-correlation method, using the same software, as described previously.
- Conditions
- COPD
- Being tested
- Moderate intensity continuous aerobic exercise (MICE), High-intensity interval aerobic exercise (HIIE)
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moderate intensity continuous aerobic exercise (MICE)Other
Patients will perform a moderate-intensity continuous aerobic exercise (MICE) protocol on a cycle ergometer that includes 20 minutes of cycling at 50%WRpeak.
High-intensity interval aerobic exercise (HIIE)Other
Patients will perform a high-intensity interval aerobic exercise (HIIE) protocol on a cycle ergometer that consists of 12 sets of 60 seconds work at 85% WRpeak followed by 60 seconds of rest.
| Study group | Role | What they receive |
|---|---|---|
| COPD Group A | Experimental | This group will perform moderate intensity continuous exercise in the 3rd visit and high intensity interval exercise in the 4th visit. Receives: Other: Moderate intensity continuous aerobic exercise (MICE); Other: High-intensity interval aerobic exercise (HIIE) |
| COPD Group B | Experimental | This group will perform high intensity interval exercise in the 3rd visit and moderate intensity continuous exercise in the 4th visit. Receives: Other: Moderate intensity continuous aerobic exercise (MICE); Other: High-intensity interval aerobic exercise (HIIE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences between MICE and HIIE protocol in brain HbO2 (changes from the baseline) during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HbO2 (changes from the baseline) during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HbO2 (changes from the baseline) during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HHb (changes from the baseline) during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HHb (changes from the baseline) during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HHb (changes from the baseline) during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain tHb (changes from the baseline) during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain tHb (changes from the baseline) during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain tHb (changes from the baseline) during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain Hbdiff (changes from the baseline) during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain Hbdiff (changes from the baseline) during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain Hbdiff (changes from the baseline) during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2 during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2 during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2 during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in Vt during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in Vt during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in Vt during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RR during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RR during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RR during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RER during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RER during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RER during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in PETCO2 during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in PETCO2 during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in PETCO2 during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE/ VCO2 during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE/ VCO2 during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE/ VCO2 during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2/HR during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2/HR during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2/HR during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SpO2 during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SpO2 during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SpO2 during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SBP during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SBP during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SBP during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in DBP during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in DBP during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in DBP during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in MAP during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in MAP during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in MAP during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in HR during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in HR during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in HR during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SV during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SV during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SV during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in CO during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in CO during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in CO during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SVR during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SVR during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SVR during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in EJT during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in EJT during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in EJT during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Secondary outcomes (6)
Differences between MICE and HIIE protocol in heart rate variability (RMSSD and SD) during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in heart rate variability (RMSSD and SD) during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in heart rate variability (RMSSD and SD) during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in BRS during rest
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in BRS during exercise
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in BRS during recovery
Measured: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2026
- Study start15 Jun 2026
- Primary completionJun 2027 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- George Papanicolaou Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aikaterini Gakidi, George Papanicolaou Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07707271
- Sponsor's protocol ID
- 8-31.04.2026 / ΔΔ5394
- Status last verified
- Sep 2026
- First submitted
- 26 Jun 2026
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Brain Oxygenation, Cadiopulmonary Parameters and Autonomic Nervous System Function During Moderate Intensity Continuous Versus High Intensity Interval Exercise in Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT07707271
- Acronym / sponsor ID
- 8-31.04.2026 / ΔΔ5394
- Conditions
- COPD
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- George Papanicolaou HospitalUniversity, hospital or other
- Study start
- 15 Jun 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 16 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic Obstructive Pulmonary Disease (COPD) is characterized by exercise intolerance, which is a prognostic factor of disease severity and mortality and is usually attributed to ventilatory limitations. Emerging evidence indicates that cerebral oxygenation may also be an important contributor, being impaired both at rest and during exercise in COPD patients. Furthermore, abnormal systemic hemodynamic responses and autonomic nervous system (ANS) dysfunction have been observed, which may further impair cerebral oxygenation. The type of exercise training applied in pulmonary rehabilitation (continuous versus interval) appears to influence these mechanisms differently, yet evidence on their impact on cerebral oxygenation in COPD remains scarce. The aim of this study is to compare, for the first time, the acute changes in cerebral oxygenation, CPET parameters, systemic hemodynamic responses, and autonomic responses in patients with COPD who undergo a high-intensity interval aerobic exercise (HIIE) protocol versus a moderate-intensity continuous aerobic exercise (MICE) protocol. These findings will have important clinical implications, as they may guide the choice of the most appropriate exercise modality in pulmonary rehabilitation.
Detailed description
This is a single-centre, prospective, randomized, cross-over clinical trial that will be conducted at "G. Papanikolaou Hospital, Thessaloniki, Greece. For the purposes of this study, COPD patients that fulfil the inclusion/exclusion criteria will be recruited from Pulmonary Outpatient Clinics of "G. Papanikolaou" General Hospital of Thessaloniki and included after signing a written informed consent form. The study protocol was approved by the Ethics Committee of the School of Medicine, Aristotle University of Thessaloniki. All procedures and evaluations will be performed according to the Declaration of Helsinki 2013 Amendment.
The study will be conducted in a total of 4 visits including baseline assessment. At baseline assessment (visit 1), all subjects will provide a detailed medical history including smoking history, comorbidities, history of acute COPD exacerbations and severity of dyspnea (based on the modified Medical Research Council dyspnea scale). Then, they will undergo a post-bronchodilation spirometry, assessment of diffusion capacity (DLCO), measurement of lung volumes and blood pressure measurements after 10min of rest. Arterial blood gases sampling (breathing room air) will be collected, to confirm lack of resting hypoxemia. Moreover, data regarding physical activity will be collected, using the short form of International Physical Activity Questionnaire (IPAQ). The eligible patients that will be recruited will be advised to refrain from food for 4h and from caffeine, alcohol, or tobacco for 12 h and receive any standard medication before their morning appointment in the research laboratory to perform the assessments described below.
Visit 2 will be conducted with a week of baseline visit. and visits 3 and 4 will take place at least 72h after visit 2. During visit 2, all recruited patients will undergo a cardiopulmonary exercise test (CPET) on a cycle ergometer using an incremental exercise RAMP protocol to exhaustion to establish peak work rate (WRpeak). For visits 3 and 4, all patients will perform in random order on different visits (separated by one week) two exercise protocols on the same cycle ergometer, a high-intensity interval aerobic exercise (HIIE) protocol and a moderate-intensity continuous aerobic exercise (MICE) protocol. The HIIE protocol will consist of 60 seconds work at 85% WRpeak followed by 60 seconds of rest and the MICE protocol will include 20 minutes of cycling at 50% WRpeak. Exercise protocols will be matched for total workload. All parameters will be recorded at rest (3 minutes), during unloaded warm-up (3 minutes), during the exercise and during 3-min recovery following the completion of exercise bouts. The rate of perceived exertion (1-10 Borg scale), legs' perceived exertion (1-10 Borg scale), dyspnea (0-10 scale), and will be assessed every 3 min and at exercise termination.
During the CPET and the protocols, respiratory gas exchange will be recorded using a metabolic cart (Ultima CPX™, MGC Diagnostics). Breath-by-breath values for minute ventilation (VE), respiratory rate (RR), tidal volume (Vt), oxygen uptake (VO2), and end-expiratory pressure of carbon dioxide (PETCO2) will be recorded, along with derived variables. Maximum Minute Ventilation (MVV) will be calculated using the formula "Forced Expiratory Volume in 1 s (FEV1) x 40". A 12-lead electrocardiogram and oxygen saturation (SpO2, finger pulse oximetry) will be continuously monitored.
For cerebral oxygenation assessment, near-infrared spectroscopy (NIRS, OxyMon, Artinis Medical Systems, Elst, the Netherlands) will continuously monitor, non-invasively, changes in cerebral oxygenation, by measuring the micromolar (μΜ) relative changes from (resting conditions for oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), total hemoglobin (tHb), and Hb-difference. The NIRS probes will be placed over the patients' left prefrontal lobe between Fp1 and F3, according to the modified international EEG 10-20 system, with the receiving sensor fixed laterally to the emitter at a distance of 4.5 cm.
Hemodynamic parameters will be continuously and non-invasively assed using a photoplethysmography apparatus (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands) connected to the participants' finger. This device allows beat-to-beat tracing of systolic and diastolic blood pressure (SBP and DBP relatively, mmHg), mean arterial pressure (MAO, mmHg) and heart rate (HR). Beat-by-beat HR and stroke volume (SV, ml) will be computed using the Modelflow method, an arterial pressure wave analysis which has been shown to be a reliable alternative to invasive thermodilution techniques at rest and during exercise. Cardiac output (CO, L/min), systemic vascular resistance (SVR, mmHg.s/mL) and ejection time (EJT, s) will be estimated using the BeatScope software (Beatscope version 1a, Finometer, Finapres Medical Systems). Autonomic responses will be assessed using the non-linear components of Heart Rate Variability (HRV) with Kubios software (Kubios, version 3.3.1, Kubios Oy, 2019). The root mean square of successive differences (RMSSD), an index of parasympathetic system activity, will be calculated. The standard deviation perpendicular to the line-of-identity SD1 (an index of parasympathetic system activity), the standard deviation along the line-of-identity (SD2) and their ratio (SD1/SD2) (an index of vagal/sympathetic function) will be analysed, since these measures are not affected by changes in respiration patterns. Baroreflex sensitivity (BRS, ms/mmHg) will be assessed by examining the spontaneous fluctuations in the blood pressure as assessed by a cross-correlation method, using the same software, as described previously.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| COPD Group A | Experimental | Other: Moderate intensity continuous aerobic exercise (MICE), Other: High-intensity interval aerobic exercise (HIIE)This group will perform moderate intensity continuous exercise in the 3rd visit and high intensity interval exercise in the 4th visit. |
| COPD Group B | Experimental | Other: Moderate intensity continuous aerobic exercise (MICE), Other: High-intensity interval aerobic exercise (HIIE)This group will perform high intensity interval exercise in the 3rd visit and moderate intensity continuous exercise in the 4th visit. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Clinical diagnosis of COPD based on smoking history (pack/years) or exposure to other risk factors and post bronchodilation forced expiratory volume (FEV1) to forced vital capacity (FVC) ratio <0.7
- Resting arterial oxygen partial pressure at room air >60 mmHg, according to recent (within a week) arterial blood gases assessment
- Disease being stable and treated optimal, based on current GOLD guidelines.
- Provision of informed written signed consent prior to study entry
Key exclusion criteria (12 listed)
- Recent respiratory infection or exacerbation (as indicated by deterioration of respiratory symptoms, hospital admission and/or change in medication within the previous month), within the past 3 months
- Changes in COPD medication with the past month
- History of asthma and/or reversible airway obstruction (post bronchodilation FEV1/ FVC >0.7)
- Pulmonary hypertension
- Congestive heart failure (Left Ventricle Ejection Fraction <50% in recent echocardiography)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Moderate intensity continuous aerobic exercise (MICE)Patients will perform a moderate-intensity continuous aerobic exercise (MICE) protocol on a cycle ergometer that includes 20 minutes of cycling at 50%WRpeak. | Other | COPD Group A, COPD Group B |
| High-intensity interval aerobic exercise (HIIE)Patients will perform a high-intensity interval aerobic exercise (HIIE) protocol on a cycle ergometer that consists of 12 sets of 60 seconds work at 85% WRpeak followed by 60 seconds of rest. | Other | COPD Group A, COPD Group B |
Primary outcome
Differences between MICE and HIIE protocol in brain HbO2 (changes from the baseline) during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HbO2 (changes from the baseline) during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HbO2 (changes from the baseline) during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HHb (changes from the baseline) during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HHb (changes from the baseline) during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain HHb (changes from the baseline) during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain tHb (changes from the baseline) during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain tHb (changes from the baseline) during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain tHb (changes from the baseline) during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain Hbdiff (changes from the baseline) during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain Hbdiff (changes from the baseline) during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in brain Hbdiff (changes from the baseline) during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2 during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2 during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2 during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in Vt during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in Vt during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in Vt during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RR during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RR during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RR during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RER during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RER during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in RER during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in PETCO2 during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in PETCO2 during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in PETCO2 during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE/ VCO2 during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE/ VCO2 during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VE/ VCO2 during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2/HR during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2/HR during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in VO2/HR during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SpO2 during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SpO2 during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SpO2 during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SBP during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SBP during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SBP during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in DBP during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in DBP during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in DBP during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in MAP during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in MAP during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in MAP during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in HR during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in HR during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in HR during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SV during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SV during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SV during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in CO during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in CO during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in CO during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SVR during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SVR during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in SVR during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in EJT during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in EJT during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in EJT during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
6 secondary outcomes
Differences between MICE and HIIE protocol in heart rate variability (RMSSD and SD) during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in heart rate variability (RMSSD and SD) during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in heart rate variability (RMSSD and SD) during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in BRS during rest
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in BRS during exercise
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Differences between MICE and HIIE protocol in BRS during recovery
Time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
George Papanikolaou General Hoapital of Thessaloniki
Thessaloniki, Greece
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Moderate intensity continuous aerobic exercise (MICE) and High-intensity interval aerobic exercise (HIIE) in people with COPD, run by George Papanicolaou Hospital at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. 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 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences between MICE and HIIE protocol in brain HbO2 (changes from the baseline) during rest (time frame: The MICE and HIIE protocols will be conducted within 2 weeks from enrollment and will be separated by one week.). The study lists 63 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Sep 2026.