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Pulmonary Adaptive Responses to HIIT in COPD

Pulmonary Adaptive Responses to HIIT in COPD

Status
UNKNOWN
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05552833
Acronym
COPDEX0
Enrollment
24
Registered
2022-09-23
Start date
2022-09-05
Completion date
2024-08-01
Last updated
2022-10-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

High intensity interval training (HIIT), Lung growth, Diffusion capacity, Blood flow, Lung tissue mass, Oxygen extraction

Brief summary

Patients with chronic obstructive lung disease (COPD) suffer from a progressive loss of lung function that leads to poor quality of life, and often invalidity and early death. Regular exercise can improve quality of life in these patients, but the health care system lack the underlying mechanism of exercise-induced improvement in COPD and it is widely thought not to have any effect on lung function. The aim of the present study is to investigate to which extent lung tissue mass and rest-to-exercise diffusion capacity changes differ in COPD patients compared to the healthy state. In order to design prospective clinical trials on the putative impact of high-intensity interval training (HIIT) investigating these parameters, and a secondary aim is to assess the feasibility of such a study in terms of patient inclusion, adherence and methodology.

Detailed description

Patients with Chronic obstructive pulmonary disease (COPD) suffer from a progressive loss of lung function that leads to poor quality of life, and often invalidity and early death. Regular exercise is considered the most effective non-pharmacological intervention for improving quality of life in these patients. However, its use is halted by the lack of understanding of the mechanism of exercise-induced improvement in COPD, and is widely thought not to have any effect on lung function in the clinical setting. Exercise is thus mainly considered a way to alleviate symptoms, primarily by improving skeletal muscle function, but without the potential to reverse the disease. Therefore, relatively short and low-intensity exercise interventions are typically prescribed and are often not pursued in patients with the greatest symptom burden. The reasoning for not prescribing exercise more widely in COPD is based on two assumptions: 1) new tissue cannot be formed in the adult lung, and 2) no consistent exercise training-induced changes in lung function have previously been documented. However, de novo tissue formation has repeatedly been demonstrated in the adult lung, both in animals and humans, primarily in response to prolonged hypoxia and pneumonectomy. It has recently been reported that interval-based training counteracts the progressive loss of lung tissue in animal models of experimental COPD. The most likely stimulus is the mechanical strain, and if any measurable changes are to be induced by training, a high-intensity interval training (HIIT) scheme is preferable to be initiated in pulmonary rehabilitation. On this basis, this study aim to conduct a prospective randomised trial, in which the impact of HIIT on lung weight (assessed by CT), rest-to-exercise diffusion capacity, 3-dimensional distribution of pulmonary perfusion measured by single photon emission computed tomography (SPECT)-low dose CT are addressed. Indeed, the latter is an especially useful clinical tool for the pathophysiological classification of COPD patients, and rest-to-exercise SPECT has the potential as a diagnostic tool that 'pinpoints' the exact cause of dyspnoea in the individual COPD patient, but has not yet been validated for this purpose. While all the methods are established, there is a need for more information regarding COPD-associated changes in lung tissue mass ('lung weight') and rest-to-exercise pulmonary diffusion changes compared to the healthy state. An assessment of the feasibility of an extended HIIT-trial using these methods in COPD patients as well as estimates of the in-study changes in the resultant physiological estimates (for the purpose of sample size estimations) is warranted.

Interventions

OTHERHigh intensity interval training

Participants will undergo 12 weeks of supervised HIIT training (3 times per week). The HIIT protocol will consist of 4x4 min.

Sponsors

Rigshospitalet, Denmark
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE

Intervention model description

12 COPD will undergo the intervention in one arm and 12 healthy, age and BMI matched individuals will undergo the same intervention.

Eligibility

Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
Yes

Inclusion criteria

-patients * Men and women * 45-80 years * COPD (GOLD stage I to III) * Forced expiratory volume in 1 sec (FEV1)/forced vital capacity ratio (FVC) \< 0.8, FEV1 \< 90% of predicted value * Modified Medical Research Council score (mMRC 0 - 3) * Resting arterial oxygenation \> 90% * Do not fulfil the physical activity recommendations by the Danish Health Authority Inclusion criteria - controls * Men and women * 45-80 years * Normal FEV1, FVC, FEV1/FVC, and single-breath diffusion capacity * Same sex, age (± 3 years) and BMI (± 10%) * Do not fulfil the physical activity recommendations by the Danish Health Authority (19) * BMI 18-35

Exclusion criteria

- patients * Symptoms of ischaemic heart disease * Known heart failure * Previous severe or current COVID-19 * Unable to complete or understand HIIT training * Claudication * Symptoms of disease within 2 weeks prior to the study * Participation in pulmonary rehabilitation within 6 months * Known malignant disease * Pregnancy * Unstable cardiac arrhythmic disease * Renal or liver dysfunction

Design outcomes

Primary

MeasureTime frameDescription
Lung tissue massCT-scans at baseline and at 12 week follow up.Change in lung weight in COPD patients compared to matched controls using CT-scans.
Rest-to-exercise diffusion capacityDLNO/CO measured at baseline and at 12 week follow up.Change in rest-to-exercise pulmonary diffusion capacity between COPD patients and matched healthy controls measured by DLNO/CO.

Secondary

MeasureTime frameDescription
Rest-to-exercise pulmonary perfusion ratio changeAt baseline and at 12 week follow upRest-to-exercise pulmonary perfusion ratio change in COPD patients compared to matched controls measured by single photon emission computed tomography (SPECT).
Rest-to-exercise leg blood flow change in COPDAt baseline and at 12 week follow upRest-to-exercise leg blood flow change in COPD patients compared to matched controls measured by ultrasound doppler in a single leg knee extensor model.

Other

MeasureTime frameDescription
Hand-grip strengthAt baseline and at 12 week follow up.Measured with a dynamometer.
Body compositionAt baseline and at 12 week follow up.total fat mass, lean body mass measured with dual energy x-ray absorption.
Lung function: FEV1At baseline and at 12 week follow up.Change in Forced expiratory volume in 1 second (FEV1) (ml)
Lung function: TLCMeasured during the 12 week intervention.Change in total lung capacity (TLC)(ml)
Lung function: FVCMeasured during the 12 week intervention.Change in forced vital capacity (FVC)(ml)
Lung function: RVMeasured during the 12 week intervention.Change in residual volume (RV) (ml)
Lung function: VAMeasured during the 12 week intervention.Change in alveolar volume (VA) (ml)
Lung function: DLCOcMeasured during the 12 week intervention.Single-breath diffusion capacity to carbon monoxide corrected for hemoglobin (ml/min/mmHg)
6-minute walking testAt baseline and at 12 week follow up.Distance transversed during 6 minutes of maximum effort walking.
Chronic obstructive pulmonary disease Assessment Test (CAT-score)At baseline and at 12 week follow up.Health-related quality of life - COPD Assessment Test, (CAT) score. Higher values meaning a smaller burden of symptoms.
Oxygen extraction in lower limb musculature during small mass exerciseAt baseline and at 12 week follow up.Calculated from paired arterial and venous blood gases obtained from intraarterial and venous catheters.
Intima media thickness in the carotid arteryAt baseline and at 12 week follow up.Measured with ultrasound.
Exercise feasibility: exercise sessions attendance rate.Measured during the 12 week intervention.Exercise attendance rate (%) defined as number of attended exercise sessions / by number of prescribed sessions x 100.
Exercise feasibility: Relative dose intensity (RDI)Measured during the 12 week intervention.RDI (%) of exercise, defined as prescribed exercise dose / performed exercise dose x 100
Exercise feasibility: early exercise terminationMeasured during the 12 week intervention.Incidence of early termination of attended exercise sessions, defined as termination of an exercise session before the prescribed exercises have been performed
Withdrawal rateMeasured during the 12 week intervention.Incidence of permanent discontinuations of the exercise intervention, defined as participants that withdraw entirely from the exercise intervention.
Exercise feasibility: Patient-reported symptomatic adverse events (paint, dizziness, nausea, fatigue, other)Measured during the 12 week intervention.Changes in patient-reported symptomatic adverse events (pain, dyspnea, fatigue, cough, sore muscles)
GlucoseAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of glucose
IL-1At baseline and at 12 week follow up.Exercise induced changes in plasma levels of interleukin 1
IL-1RAAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of interleukin-1 receptor antagonist
TNF-alfaAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of tumor necrosis factor alfa
IL-6At baseline and at 12 week follow up.Exercise induced changes in plasma levels of interleukin-6
IL-10At baseline and at 12 week follow up.Exercise induced changes in plasma levels of interleukin 10
AdiponectinAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of adiponectin
IL-15At baseline and at 12 week follow up.Exercise induced changes in plasma levels of interleukin 15
HS-CRPAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of high sensitive c-reactive protein
HDLAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of High density lipoprotein
LDLAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of low density lipoprotein
InsulinAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of insulin
CreatinineAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of creatinine
LeptinAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of leptin
CarbamideAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of carbamide
Rest-to-exercise cardiac output changeAt baseline and at 12 week follow upCardiac output measured by oxygen pulse.
LeucocytesAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of leucocytes
ALATAt baseline and at 12 week follow up.Exercise induced changes in plasma levels of alanine-aminotransferase
VO2peak (and estimated VO2max)At baseline and at 12 week follow upIncremental exercise test on bike ergometer with COSMED system using breath by breath analysis.
VO2 verification boutAt baseline and at 12 week follow upConfirmation of maximum oxygen consumption measured 20 minutes after intitial VO2 peak test at a 110 % of maximum workload.
The maximal workload (knee extension)At baseline and at 12 week follow up.Incremental exercise test on one leg knee extensor chair.

Countries

Denmark

Contacts

Primary ContactRonan Martin Griffin Berg, MD
ronan.martin.griffin.berg@regionh.dk(+45) 3545 7641
Backup ContactJacob Peter Hartmann, MD
jacob.peter.okholm.hartmann.01@regionh.dk40924285

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 5, 2026