Tissue Regeneration in Patients With Chronic Obstructive Pulmonary Disease After an Exercise Intervention. (T-Rex)

Activation of Regenerative Pathways by Exercise Training in Patients With Chronic Obstructive Pulmonary Disease

The main objective of this project is to identify mechanisms for lung regeneration in patients with COPD induced by exercise training. The hypothesis is that adjusted exercise training improves disease outcome in these patients by decrease remodelling processes linked to oxidative stress, inflammatory and/or immunological pathways in the lung. Along the way, the investigator also expect to identify (or validate) biomarkers mirroring systemic processes such as reduced inflammation and ameliorating the epithelial barrier in these patients. These events may additionally act as potential targets for interventions.

Objectives (i) Evaluate biomarkers for regenerative processes, matrix turnover, stem cell activity and inflammatory patterns in lung tissue biopsies, blood- and urine samples correlated to vital lung parameters and physical capacity, before and after attending an exercise-training program.

(ii) Study the effects of exercise training on the pulmonary ventilation/perfusion ratio and quality of life.

(iii) Evaluate the relation between pathophysiology in the lung evaluated by CT scan, and systemic response measured by muscle biopsies and biomarkers in blood/urine.

(iv) Investigate in vitro cell behaviour and remodelling/regenerative processes altered in COPD patients upon exercise training (aim 1).

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Other: Exercise regime

Detailed Description

Chronic obstructive pulmonary disease (COPD) is an increasing worldwide health problem characterized by progressive destruction of lung tissue. In the shadow of the pandemic, COPD patients may suffer more severely from COVID-19 with worse prognosis and higher mortality rate. This may be due to common underlying risk factors such as smoking, cardiovascular disease and a sedative life style. To cope with the soaring burden on the health care system posed by the aftermath of the pandemic in the context of chronic diseases such as COPD, the importance of self-responsibility to increase quality of life is emerging. New guidelines from the 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease support exercise in the management of COPD and after COVID-19 infection, even during mild COVID-19 symptoms. However, little is known about the molecular alterations induced by exercise training and how to boost the body´s ability to halt disease progression in COPD.

The hypothesize is that adjusted exercise training increases the ability to cope with biological stress, which is increased in COPD due to i.e. chronic inflammation and a history of smoking, and may facilitate restoration of damaged tissue. In this proposal the anticipation is to link the effects of physical exercise to amelioration of vital lung parameters, physical strength including 6 min walk test, and quality of life, by evaluating biomarkers for stem cell activity, regeneration and inflammation in lung tissue biopsies and blood samples. This will also result in the recognition of pathways that are targetable for novel pharmaceuticals that could synergize with the training effect.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden
    • Recruiting
    • Lund University
    • Contact: Gunilla Westergren Thorsson, Phd; Phone Number: +4646222 00 00; Email: gunilla.westergren-thorsson@med.lu.se
    • Contact: Caroline Ms Larsson, Phd; Phone Number: +46736673026; Email: caroline.larsson@med.lu.se
  • Uppsala, Sweden
    • Recruiting
    • Uppsala University
    • Contact: Margareta Mrs Emtner, Phd; Phone Number: +46737594481; Email: margareta.emtner@medsci.uu.se
    • Contact: Christer Mr Janson, Phd; Phone Number: +46186114115; Email: christer.janson@medsci.uu.se

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Forced expiratory volume in one second (FEV1) 85-30 % of predicted post bronchodilator
• Optimal medical treatment according to GOLD and the Swedish National Guidelines
• Absence of other significant diseases that could contribute to physical exercise limitation
• Non-smoking since at least one year
• Free from exacerbations (last 4 weeks)
• BMI = 18- 35

Exclusion Criteria:

• Regular participation in adjusted/specially designed exercise sessions
• Unstable cardiovascular or pulmonary disease
• Smoking
• Any other criteria that at the discretion of the investigator prevent the study subject from participating in an exercise-training program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Exercise; The exercise training protocol to be used in this study: Supervised exercise training (aerobic- and muscle strengthening exercise): 2 times a week for 12 weeks.; Aerobic exercise with ergometer cycling for 30 min, at moderate intensity (60% Wpeak) individually adjusted to level 4-6 on the Borg category ratio-10 scale.; Muscle strengthening exercise will consist of 8-12 strength exercises of the major upper and lower body muscle groups. Each exercise includes three sets with 8-12 repetitions. Exercise training at home: once a week for 12 weeks.

Other: Exercise regime; Exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Function	FEV1 (Forced Expiratory volume in one second)	Baseline, post intervention at 12 wks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical capacity	6MWD (six-minute walk distance), longer distance = better health	Baseline, post intervention at 12 wks
Inflammation markers	Biomarkers (eg. C reactive protein, Interleukin-6)	Baseline, post intervention at 12 wks
Level of emphysema	HRCT, (high-resolution computed tomography), AiDA (Air space dimension assessment)	Baseline, post intervention at 12 wks
Maximal physical capacity ( Wmax)	Maximal watt during incremental cardiopulmonary exercise test	Baseline, post intervention at 12 wks
COPD Assessment Test (CAT)	Health status, Score 1-40, lower score = better health	Baseline, post intervention at 12 wks

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Lund University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; Chronic obstructive pulmonary disease; Regeneration
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: Dnr 2022-00831-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No