To investigate the physiological and structural adaptations of peripheral muscle function at a cellular level in response to EBV treatment.
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is to assess the physiological adaptations,
in terms of cellular bioenergetics, of the quadriceps muscle in patients with
severe COPD in response to EBV treatment. This will be done by performing
31P-MRS during exercise testing in a MR-compatible ergometer at baseline and at
6 months follow-up, for which the following outcomes will be assessed:
- Quadriceps phosphocreatine concentration (PCr) at rest and during progressive
exercise;
- Quadriceps inorganic phosphorus concentration (Pi) at rest and during
progressive exercise;
- Quadriceps pH at rest and during progressive exercise;
- Post-exercise recovery rate of quadriceps PCr, Pi and pH.
Secondary outcome
The secondary endpoint of this study is to investigate in muscle biopsies the
following outcomes:
- Change in muscle fiber type composition 6 months after EBV treatment.
- Change in mitochondrial density 6 months after EBV treatment.
- Change in master regulators of muscle oxidative programming 6 months after
EBV treatment.
- Change in mitochondrial respiration 6 months after EBV treatment.
- Change in lipid droplets 6 months after EBV treatment.
- Change in mRNA and protein expression of markers of inflammation and hypoxia
induced signalling 6 months after EBV treatment.
- Change in regulators of muscle protein turnover 6 months after EBV treatment.
Background summary
Chronic obstructive pulmonary disease (COPD) is characterised by a high
prevalence of peripheral muscle dysfunction, which can have significant
clinical consequences, including decreased exercise capacity, reduced quality
of life, and even a higher mortality rate. Reduction of lung hyperinflation
using bronchoscopic lung volume reduction treatment with Pulmonx Zephyr one-way
endobronchial valves (EBV) is a minimally invasive intervention which improves
exercise capacity and physical activity in patients with severe emphysema. This
positive effect is also related to weight gain and alterations in body
composition. To our knowledge, the physiologic and structural adaptations of
skeletal muscle function after EBV treatment has never been investigated
before.
Study objective
To investigate the physiological and structural adaptations of peripheral
muscle function at a cellular level in response to EBV treatment.
Study design
A single center, exploratory, prospective clinical study with a single-arm
pretest-posttest design. Patients with severe emphysema who will receive a
bronchoscopic lung volume reduction treatment are asked to undergo additional
in-magnet exercise testing and muscle biopsies before and after placement of
EBVs.
Study burden and risks
This study has no specific benefits for the participating patients and the
study also has no major risks. The patients will be exposed to additional
exercise capacity and physical activity measurements. Imaging by means of
31P-MRS has previously been shown to be safe and is already widely used in
different studies. Patients are not exposed to any radiation and/or contrast
agents. Moreover, patients will undergo two muscle biopsies. Muscle biopsy can
cause a small local haematoma or infection, however, the occurrence of both is
very low and the risks will be minimalized.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
1. Patient is scheduled for a bronchoscopic lung volume treatment using Pulmonx
Zephyr one-way endobronchial valves;
2. Patient read, understood and signed the Informed Consent Form.
Exclusion criteria
1. Inability to perform a cycle ergometry test;
2. Contraindications for undergoing a magnetic resonance imaging scan (e.g.
claustrophobia, implanted cardiac devices);
3. Body length >190cm;
4. Use of any anticoagulant therapy;
5. COPD exacerbation 4 weeks prior to testing.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT06025500 |
| CCMO | NL85100.042.23 |