COPDEX0: Pulmonary Adaptive Responses to HIIT in COPD

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Recruiting

CT.gov ID

NCT05552833

Collaborator

(none)

Enrollment

Locations

Arms

22.9

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Other: High intensity interval training	N/A

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:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

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

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Pulmonary Adaptive Responses to HIIT in COPD

Actual Study Start Date :

Sep 5, 2022

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: COPD patients This arm will consist of only COPD patients.	Other: High intensity interval training Participants will undergo 12 weeks of supervised HIIT training (3 times per week). The HIIT protocol will consist of 4x4 min.
Experimental: Healthy controls This arm will consist of age and BMI matched healthy controls.	Other: High intensity interval training Participants will undergo 12 weeks of supervised HIIT training (3 times per week). The HIIT protocol will consist of 4x4 min.

Arm

Intervention/Treatment

Experimental: COPD patients

This arm will consist of only COPD patients.

Other: High intensity interval training

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

Experimental: Healthy controls

This arm will consist of age and BMI matched healthy controls.

Other: High intensity interval training

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

Outcome Measures

Primary Outcome Measures

Lung tissue mass [CT-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 capacity [DLNO/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 Outcome Measures

Rest-to-exercise pulmonary perfusion ratio change [At baseline and at 12 week follow up]
Rest-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 COPD [At baseline and at 12 week follow up]
Rest-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 Outcome Measures

Rest-to-exercise cardiac output change [At baseline and at 12 week follow up]
Cardiac output measured by oxygen pulse.
VO2peak (and estimated VO2max) [At baseline and at 12 week follow up]
Incremental exercise test on bike ergometer with COSMED system using breath by breath analysis.
VO2 verification bout [At baseline and at 12 week follow up]
Confirmation 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.
Hand-grip strength [At baseline and at 12 week follow up.]
Measured with a dynamometer.
Body composition [At baseline and at 12 week follow up.]
total fat mass, lean body mass measured with dual energy x-ray absorption.
Lung function: FEV1 [At baseline and at 12 week follow up.]
Change in Forced expiratory volume in 1 second (FEV1) (ml)
Lung function: TLC [Measured during the 12 week intervention.]
Change in total lung capacity (TLC)(ml)
Lung function: FVC [Measured during the 12 week intervention.]
Change in forced vital capacity (FVC)(ml)
Lung function: RV [Measured during the 12 week intervention.]
Change in residual volume (RV) (ml)
Lung function: VA [Measured during the 12 week intervention.]
Change in alveolar volume (VA) (ml)
Lung function: DLCOc [Measured during the 12 week intervention.]
Single-breath diffusion capacity to carbon monoxide corrected for hemoglobin (ml/min/mmHg)
6-minute walking test [At 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 exercise [At 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 artery [At 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 termination [Measured 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 rate [Measured 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)
Glucose [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of glucose
IL-1 [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of interleukin 1
IL-1RA [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of interleukin-1 receptor antagonist
TNF-alfa [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of tumor necrosis factor alfa
IL-6 [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of interleukin-6
IL-10 [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of interleukin 10
Adiponectin [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of adiponectin
IL-15 [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of interleukin 15
HS-CRP [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of high sensitive c-reactive protein
HDL [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of High density lipoprotein
LDL [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of low density lipoprotein
Insulin [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of insulin
Creatinine [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of creatinine
Leptin [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of leptin
Carbamide [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of carbamide
ALAT [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of alanine-aminotransferase
Leucocytes [At baseline and at 12 week follow up.]
Exercise induced changes in plasma levels of leucocytes

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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