Tissue Regeneration in Patients With Chronic Obstructive Pulmonary Disease After an Exercise Intervention.

Chronic Obstructive Pulmonary Disease Clinical Trial

— T-Rex  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06335992
• Other study ID #: Dnr 2022-00831-01
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: March 2024
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: April 30, 2025
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• Exercise regime
Exercise

Locations

Country	Name	City	State
Sweden	Lund University	Lund
Sweden	Uppsala University	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	Lund University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary Function	FEV1 (Forced Expiratory volume in one second)	Baseline, post intervention at 12 wks
Secondary	Physical capacity	6MWD (six-minute walk distance), longer distance = better health	Baseline, post intervention at 12 wks
Secondary	Inflammation markers	Biomarkers (eg. C reactive protein, Interleukin-6)	Baseline, post intervention at 12 wks
Secondary	Level of emphysema	HRCT, (high-resolution computed tomography), AiDA (Air space dimension assessment)	Baseline, post intervention at 12 wks
Secondary	Maximal physical capacity ( Wmax)	Maximal watt during incremental cardiopulmonary exercise test	Baseline, post intervention at 12 wks
Secondary	COPD Assessment Test (CAT)	Health status, Score 1-40, lower score = better health	Baseline, post intervention at 12 wks