Muscle Function After Lung Transplantation in Patients With Chronic Obstructive Pulmonary Disease (COPD) (COPD)

The purpose of the project is to investigate changes in the quadriceps muscle and cardiovascular regulation during exercise in relation to improved lung function after lung transplantation in patients with COPD.

Study Overview

• Status: Unknown
• Conditions: COPD
• Intervention / Treatment: Other: Lung transplantation

Detailed Description

Dysfunctional skeletal musculature of the lower limbs is related to low quality of life, exercise intolerance and higher mortality in patients with COPD. Limb muscle dysfunction in COPD consists of muscle atrophy and reduced muscle strength but also intra-muscular alterations in oxidative capacity and mitochondrial function are often present. Moreover, reduced blood flow to exercising muscle may also contribute to the muscle dysfunction in COPD. The mechanisms responsible for muscle dysfunction in COPD patients remain unclear but could be a consequence of reduced lung function, inflammation, medications or low physical activity. Loss of lung function with COPD is normally irreversible so the transition to near-normal lung function after lung transplantation is a unique model to investigate the adaptation of the limb muscle to improved lung function. Thus, the purpose of this project is to investigate the effect of lung transplantation on limb muscle function (mitochondrial function, oxidative enzyme capacity, fiber type distribution, oxygen delivery/uptake) and daily physical activity level in patients with COPD. The project has a translational focus on muscle dysfunction in COPD and uses methodologies from clinical medicine, integrative physiology and molecular biochemistry in order to gain knowledge of mechanisms behind limb muscle dysfunction and exercise intolerance in COPD.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Ulrik Winning Iepsen, MD, PhD; Phone Number: +4540732842; Email: ulrik_winning@hotmail.com
• Study Contact Backup: Name: Camilla Koch Ryrsø, MSc; Email: ryrsoe@yahoo.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • the Centre for Physical Activity Research, Copenhagen University Hospital
    • Contact: Ulrik Winning Iepsen, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

COPD patients on the waiting list for a lung transplantation

Description

Inclusion Criteria:

• COPD with or without alpha 1-antitrypsin deficiency on the waiting list for a lung transplantation
• Single or double lung transplantation
• ≥ 18 years
• Ability to give informed consent

Exclusion Criteria:

• Retransplantation
• Multiple-organ transplantation (heart-lung transplantation)
• Musculoskeletal disorders which substantially inhibits physical activity
• Need for crossmatching in connection with lung transplantation
• Anticoagulant therapy before lung transplantation (except acetylsalicylic acid)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COPD patients; COPD patients on the waiting list for a lung transplantation	Other: Lung transplantation; Single or double lung transplantation in patients with COPD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in leg blood flow (mL/min)	Endothelium function will be evaluated during acute exercise (one legged kicking) by Flow doppler	Change from baseline at 6 months
Change in 6 min walking test	Exercise capacity	Change from baseline at 6 months
Change in health-related quality of life	Health-related quality of life will be assessed by total mean score of St. George's Respiratory Questionnaire (SGRQ) (2 parts,3 components questionnaire). Scores range from 0 to 100, with higher scores indicating more limitations. A minimum change in score of 4 units are considered clinically relevant.	Change from baseline at 6 months
Change in health-related quality of life	Health-related quality of life will be assessed by mean score of a validated Danish version of the COPD Assessment Test (CAT). The CAT is a short 8-item questionnaire with scoring range of 0-40, where higher scores indicating more limitations. A change of 2 units suggests a meaningful difference.	Change from baseline at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in skeletal muscle function	Muscle biopsy	Change from baseline at 6 months
Change in blood volume	CO re-breathing method	Change from baseline at 6 months
Change in capillarization of lung tissue	Transbronchial biopsy (only COPD patients)	Change from baseline at 6 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Ulrik Winning Iepsen, MD, PhD, Centre for Physical Activity Research, Copenhagen University Hospital, Copenhagen, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2018
• Primary Completion (Anticipated): April 30, 2020
• Study Completion (Anticipated): May 30, 2020

Study Registration Dates

• First Submitted: May 9, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 7, 2018

Study Record Updates

• Last Update Posted (Actual): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Cardiovascular regulation; Muscle dysfunction; Lung transplantation (LTx)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: H-17039327

Drug and device information, study documents

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