Cardiopulmonary Adaptations to High-intensity Interval Training (HIIT) in COPD (COPDEX)

Cardiopulmonary Adaptations to High-intensity Interval Training (HIIT) in COPD: a Randomized Controlled Trial (the COPDEX Study)

The aim of this prospective randomised controlled trial in which the impact of high intensity interval training (HIIT) on pulmonay blood volume, pulmonary gas exchange during exercise, and lung tissue mass.

The primary objective is to investigate whether 6 months of supervised HIIT leads to an increase in pulmonary blood volume in patients with COPD with a concomitant improvement in pulmonary gas exchange.

Key objectives are to determine whether an increase in pulmonary blood volume is associated with the formation of new lung tissue. Other secondary objectives include investigating the effect of supervised HIIT on formation of lung tissue, symptom severity, pulmonary gas exchange at supine rest and on pulmonary blood volume at rest. Finally, exploratory objectives include investigating the effects of HIIT on lung function, V̇O2peak, functional outcomes, body composition, blood samples and cardiac output.

Participants will be randomly allocated (1:1) stratified by sex to either

1. 24 weeks of HIIT training consisting of 3 weekly supervised exercise sessions or
2. A control group who will not undergo HIIT training. The control group will be encouraged not to change their exercise or eating habits.

The participants will visit the clinic pre- and post the intervention. Exercise habits, adverse events, hospital admisseions, infections and medications will be assessed by phone at week 4, 8, 12, 16, 20 and at follow-up visit. All participants will undergo 24-h accelerometry for five consecutive days to measure posture allocation and daily physical activity behavior. The devices will be attached just before the randomization, after one month, at 12 weeks and just before the 6 months testing.

Study Overview

• Status: Recruiting
• Conditions: Rehabilitation; COPD
• Intervention / Treatment: Behavioral: High Intensity Interval Training (HIIT)

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Iben E Rasmussen, MSc; Phone Number: 61698192; Email: iben-er@hotmail.com
• Study Contact Backup: Name: Ronan Berg, MD, DMSc; Phone Number: 35451825; Email: ronan.martin.griffin.berg@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Center For Physical Activity Research, Rigshospitalet
    • Contact: Iben E Rasmussen, MSc; Phone Number: 61698192; Email: iben.elmerdahl.rasmussen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Men and women
• Age >=40 and <80 years
• COPD (GOLD stage I to III)
• Modified Medical Research Council score (mMRC) of 0 to 3
• Resting arterial oxygenation > 90% Exclusion criteria
• Symptoms of ischaemic heart disease
• Known heart failure
• Unable to complete or understand HIIT training
• Claudication
• Symptoms of disease within 2 weeks prior to the study
• Participation in pulmonary rehabilitation within 3 months
• Known malignant disease
• Pregnancy
• Unstable cardiac arrhythmic disease

• Renal or liver dysfunction

  • Known chronic kidney or liver disease
  • Elevated creatinine, urea, alanine transaminase (ALAT), aspartate transaminase (ASAT), bilirubin, basic phosphatases at blood test
• Completion of pulmonary rehabilitation within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise; The HIIT intervention includes three supervised sessions per week over a 24-week period i.e., 72 exercise sessions and take place at CFAS or at home with supervision	Behavioral: High Intensity Interval Training (HIIT); The HIIT intervention consist of 4 intervals with each lasting 4 minutes (4x4min). If a participant reports discomfort related to the length of the intervals or start to feel unmotivated by performing the same exercise, we will use another HIIT protocol: 10x1min. The 4x4min HIIT consists of a warm-up period of 10 minutes with a target heart rate at 60-70% of HRmax, followed by 4 HIIT intervals with a target HR ≥85%. The intervals are separated by three minutes of active rest, in which the HR should drop to 60% of maximum. Following this, a cool down period of three minutes at warm up intensity is performed. The 10x1min HIIT consists of a 10-minute warm-up period.The warm-up is followed by 10 intervals, each lasting 1 min at 100% of maximal workload, separated by three minutes of active rest, in which the HR should drop to 60% of maximum. Following the intervals, a cool down period of three minutes at warm up intensity is performed.
No Intervention: Control group; Controls will be encouraged to maintain current exercise habits for the duration of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary blood volume (mL) at rest	Difference in change from baseline to six months between groups in pulmonary blood volume (mL) at rest	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DL,NO (mmol/(min kPa)) as a function of V̇O2 measured at rest	Difference in change from baseline to six months between groups in DL,NO (mmol/(min kPa)) as a function of V̇O2 measured at rest, 60% of current maximal workload (relative), and at follow-up including 60% of maximal workload at baseline (absolute)	6 months
Total LTM (g)	Difference in change from baseline to six months between groups in total LTM (g)	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DL,NO (mmol/(min kPa)) during exercise at 60% of current maximal workload (relative)	Difference in change from baseline to six months between groups in DL,NO (mmol/(min kPa)) during exercise at 60% of current maximal workload (relative)	6 months
DL,NO (mmol/(min kPa)) during exercise at 60% of the maximal workload measured at baseline (absolute)	Difference in change from baseline to six months between groups in DL,NO (mmol/(min kPa)) during exercise at 60% of the maximal workload measured at baseline (absolute)	6 months
Pulmonary blood volume / total blood volume ratio	Difference in change from baseline to six months between groups in pulmonary blood volume / total blood volume ratio	6 months
Health-related quality of life - COPD Assessment Test (CAT) score	Difference in change from baseline to six months between groups in health-related quality of life	6 months
Health-related quality of life - St. George's Respiratory Questionnaire (SGRQ)	Difference in change from baseline to six months between groups in health-related quality of life	6 months
Lobar LTM (g)	Difference in change from baseline to six months between groups in lobar LTM (g)	6 months
LTM/1.73 m2 BSA (g/m2)	Difference in change from baseline to six months between groups in LTM/1.73 m2 BSA (g/m2)	6 months
Total blood volume	Difference in change from baseline to six months between groups in total blood volume	6 months
DL,NO (mmol/(min kPa)) during upright rest	Difference in change from baseline to six months between groups in DL,NO (mmol/(min kPa)) during upright rest	6 months
DL,CO,5s (mmol/(min kPa)) during upright rest	Difference in change from baseline to six months between groups in DL,CO,5s (mmol/(min kPa)) during upright rest	6 months
Pulmonary capillary blood volume (VC, mL) during upright rest	Difference in change from baseline to six months between groups in pulmonary capillary blood volume (VC, mL) during upright rest	6 months
Alveolar-capillary membrane diffusing capacity (DM, mmol/(min kPa)) during upright rest	Difference in change from baseline to six months between groups in alveolar-capillary membrane diffusing capacity (DM, mmol/(min kPa)) during upright rest	6 months
DL,NO (mmol/(min kPa)) during supine rest	Difference in change from baseline to six months between groups in DL,NO (mmol/(min kPa)) during supine rest	6 months
DL,CO,5s (mmol/(min kPa)) during supine rest	Difference in change from baseline to six months between groups in DL,CO,5s (mmol/(min kPa)) during supine rest	6 months
Pulmonary capillary blood volume (VC, mL) during supine rest	Difference in change from baseline to six months between groups in pulmonary capillary blood volume (VC, mL) during supine rest	6 months
Alveolar-capillary membrane diffusing capacity (DM, mmol/(min kPa)) during supine rest	Difference in change from baseline to six months between groups in alveolar-capillary membrane diffusing capacity (DM, mmol/(min kPa)) during supine rest	6 months
Cardiac output (L/min) during exercise	Difference in change from baseline to six months between groups in cardiac output (L/min) during exercise at 60% of current maximal workload and 60% of baseline maximal workload, in the supine position, and during upright rest	6 months
DL,CO,NO-based V̇O2 during exercise	DL,CO,NO-based V̇O2 during exercise at 60% of current maximal workload and 60% of baseline maximal workload, in the supine position, and during upright rest	6 months
V̇O2peak	Difference in change from baseline to six months between groups in relative (mL/kg/min) and absolute (mL/min) V̇O2peak, ventilatory threshold (%), and ventilatory reserve (%)	6 months
Time constant (s)	Difference in change from baseline to six months between groups in time constant from V̇O2kinetic test	6 months
Amplitude (ml/kg^-1/min^-1)	Difference in change from baseline to six months between groups in amplitude measured by V̇O2kinetic test	6 months
Time delay (s)	Difference in change from baseline to six months between groups in time delay measured by V̇O2kinetic test	6 months
Hand-grip strength (kg)	Difference in change from baseline to six months between groups in hand-grip strength (kg)	6 months
Sit-to-stand test (n)	Difference in change from baseline to six months between groups in numbers of completed 30 seconds sit-to-stand test (n)	6 months
Body composition:	Difference in change from baseline to six months between groups in body composition: total mass (kg), total fat mass (kg and %), lean body mass (kg), fat percentage (%)	6 months
Lung function	Difference in change from baseline to six months between groups in lung function: FEV1 (L and %pred), FVC (L and %pred), RV (L and %pred), TLC (L and %pred), single-breath diffusion capacity to carbon monoxide (mmol/(min kPa) and %pred)	6 months
6-minute walking test	Difference in change in the distance (m) walked from baseline to six months between groups in a 6-minute walking test	6 months
Blood samples	Difference in change from baseline to six months between groups in exercise-induced cytokine responses (interleukin-6 (pg/mL), tumour necrosis factor-α (pg/mL), C-reactive protein (μg/mL), interleukin-8 (pg/mL), and interleukin-10 (pg/mL))	6 months
Mean bolus transit time (s) (supine rest)	Difference in change from baseline to six months between groups in mean bolus transit time (s) (supine rest)	6 months
Mean bolus transit time (s) (adenosine infusion)	Difference in change from baseline to six months between groups in mean bolus transit time (s) (adenosine infusion)	6 months
Global coronary flow reserve (mL/min)	Difference in change from baseline to six months between groups in global coronary flow reserve (mL/min)	6 months
Pulmonary blood volume reserve (mL)	Difference in change from baseline to six months between groups in pulmonary blood volume reserve (mL)	6 months
Left ventricular ejection fraction (%)	Difference in change from baseline to six months between groups in left ventricular ejection fraction (%)	6 months
Cardiac output (L/min) (supine rest)	Difference in change from baseline to six months between groups in cardiac output (L/min) (supine rest)	6 months
Cardiac output (L/min) (adenosine infusion)	Difference in change from baseline to six months between groups in cardiac output (L/min) (adenosine infusion)	6 months
Total plasma volume	Difference in change from baseline to six months between groups in total plasma volume	6 months
Red blood cells	Difference in change from baseline to six months between groups in red blood cells	6 months
Coronary calcium score	Difference in change from baseline to six months between groups in coronary calcium score	6 months
Intima-media thickness (IMT) in the common carotid artery (mm)	Difference in change from baseline to six months between groups in intima-media thickness (IMT) in the common carotid artery (mm)	6 months
Blood samples	Difference in change from baseline to six months between groups in blood samples: lipids (cholesterol (mmol/l), LDL (mmol/l), HDL (mmol/l)), HbA1C (mmol/l), HsCRP (mg/L), pro-BNP (pmol/L), and TSH (10-3 IU/L)	6 months
Resistance (Rrs, R5-R20)	Difference in change from baseline to six months between groups in resistance (Rrs, R5-R20) measured by IOS	6 months
Reactance (Xrs, X5)	Difference in change from baseline to six months between groups in reactance (Xrs, X5) measured by IOS	6 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: August 12, 2024
• First Posted (Actual): August 13, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: H-24021751

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No