Pulmonary Adaptive Responses to HIIT in COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

— COPDEX0  

Official title:

Pulmonary Adaptive Responses to HIIT in COPD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05552833
• Other study ID #: COPDEX0
• Status: Recruiting
• Phase: N/A
• Start date: September 5, 2022
• Est. completion date: August 1, 2024

Study information

• Verified date: October 2022
• Source: Rigshospitalet, Denmark
• Contact: Ronan Martin Griffin Berg, MD
• Phone: (+45) 3545 7641
• Email: ronan.martin.griffin.berg[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

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

Exclusion criteria - controls

• COPD

• Asthma

• Known ischaemic heart disease

• Known heart failure

• Previous severe or current COVID-19

• Unable to complete or understand HIIT training

• Symptoms of disease within 2 weeks prior to the study

• Known malignant disease

• Claudication

• Pregnancy

• Unstable cardiac arrhythmic disease

• Renal or liver dysfunction

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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.

Locations

Country	Name	City	State
Denmark	Centre for Physical Activity Research (CFAS)	Copenhagen
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rest-to-exercise cardiac output change	Cardiac output measured by oxygen pulse.	At baseline and at 12 week follow up
Other	VO2peak (and estimated VO2max)	Incremental exercise test on bike ergometer with COSMED system using breath by breath analysis.	At baseline and at 12 week follow up
Other	VO2 verification bout	Confirmation of maximum oxygen consumption measured 20 minutes after intitial VO2 peak test at a 110 % of maximum workload.	At baseline and at 12 week follow up
Other	The maximal workload (knee extension)	Incremental exercise test on one leg knee extensor chair.	At baseline and at 12 week follow up.
Other	Hand-grip strength	Measured with a dynamometer.	At baseline and at 12 week follow up.
Other	Body composition	total fat mass, lean body mass measured with dual energy x-ray absorption.	At baseline and at 12 week follow up.
Other	Lung function: FEV1	Change in Forced expiratory volume in 1 second (FEV1) (ml)	At baseline and at 12 week follow up.
Other	Lung function: TLC	Change in total lung capacity (TLC)(ml)	Measured during the 12 week intervention.
Other	Lung function: FVC	Change in forced vital capacity (FVC)(ml)	Measured during the 12 week intervention.
Other	Lung function: RV	Change in residual volume (RV) (ml)	Measured during the 12 week intervention.
Other	Lung function: VA	Change in alveolar volume (VA) (ml)	Measured during the 12 week intervention.
Other	Lung function: DLCOc	Single-breath diffusion capacity to carbon monoxide corrected for hemoglobin (ml/min/mmHg)	Measured during the 12 week intervention.
Other	6-minute walking test	Distance transversed during 6 minutes of maximum effort walking.	At baseline and at 12 week follow up.
Other	Chronic obstructive pulmonary disease Assessment Test (CAT-score)	Health-related quality of life - COPD Assessment Test, (CAT) score. Higher values meaning a smaller burden of symptoms.	At baseline and at 12 week follow up.
Other	Oxygen extraction in lower limb musculature during small mass exercise	Calculated from paired arterial and venous blood gases obtained from intraarterial and venous catheters.	At baseline and at 12 week follow up.
Other	Intima media thickness in the carotid artery	Measured with ultrasound.	At baseline and at 12 week follow up.
Other	Exercise feasibility: exercise sessions attendance rate.	Exercise attendance rate (%) defined as number of attended exercise sessions / by number of prescribed sessions x 100.	Measured during the 12 week intervention.
Other	Exercise feasibility: Relative dose intensity (RDI)	RDI (%) of exercise, defined as prescribed exercise dose / performed exercise dose x 100	Measured during the 12 week intervention.
Other	Exercise feasibility: early exercise termination	Incidence of early termination of attended exercise sessions, defined as termination of an exercise session before the prescribed exercises have been performed	Measured during the 12 week intervention.
Other	Withdrawal rate	Incidence of permanent discontinuations of the exercise intervention, defined as participants that withdraw entirely from the exercise intervention.	Measured during the 12 week intervention.
Other	Exercise feasibility: Patient-reported symptomatic adverse events (paint, dizziness, nausea, fatigue, other)	Changes in patient-reported symptomatic adverse events (pain, dyspnea, fatigue, cough, sore muscles)	Measured during the 12 week intervention.
Other	Glucose	Exercise induced changes in plasma levels of glucose	At baseline and at 12 week follow up.
Other	IL-1	Exercise induced changes in plasma levels of interleukin 1	At baseline and at 12 week follow up.
Other	IL-1RA	Exercise induced changes in plasma levels of interleukin-1 receptor antagonist	At baseline and at 12 week follow up.
Other	TNF-alfa	Exercise induced changes in plasma levels of tumor necrosis factor alfa	At baseline and at 12 week follow up.
Other	IL-6	Exercise induced changes in plasma levels of interleukin-6	At baseline and at 12 week follow up.
Other	IL-10	Exercise induced changes in plasma levels of interleukin 10	At baseline and at 12 week follow up.
Other	Adiponectin	Exercise induced changes in plasma levels of adiponectin	At baseline and at 12 week follow up.
Other	IL-15	Exercise induced changes in plasma levels of interleukin 15	At baseline and at 12 week follow up.
Other	HS-CRP	Exercise induced changes in plasma levels of high sensitive c-reactive protein	At baseline and at 12 week follow up.
Other	HDL	Exercise induced changes in plasma levels of High density lipoprotein	At baseline and at 12 week follow up.
Other	LDL	Exercise induced changes in plasma levels of low density lipoprotein	At baseline and at 12 week follow up.
Other	Insulin	Exercise induced changes in plasma levels of insulin	At baseline and at 12 week follow up.
Other	Creatinine	Exercise induced changes in plasma levels of creatinine	At baseline and at 12 week follow up.
Other	Leptin	Exercise induced changes in plasma levels of leptin	At baseline and at 12 week follow up.
Other	Carbamide	Exercise induced changes in plasma levels of carbamide	At baseline and at 12 week follow up.
Other	ALAT	Exercise induced changes in plasma levels of alanine-aminotransferase	At baseline and at 12 week follow up.
Other	Leucocytes	Exercise induced changes in plasma levels of leucocytes	At baseline and at 12 week follow up.
Primary	Lung tissue mass	Change in lung weight in COPD patients compared to matched controls using CT-scans.	CT-scans at baseline and at 12 week follow up.
Primary	Rest-to-exercise diffusion capacity	Change in rest-to-exercise pulmonary diffusion capacity between COPD patients and matched healthy controls measured by DLNO/CO.	DLNO/CO measured at baseline and at 12 week follow up.
Secondary	Rest-to-exercise pulmonary perfusion ratio change	Rest-to-exercise pulmonary perfusion ratio change in COPD patients compared to matched controls measured by single photon emission computed tomography (SPECT).	At baseline and at 12 week follow up
Secondary	Rest-to-exercise leg blood flow change in COPD	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.	At baseline and at 12 week follow up