Clinical trial NCT06025500: Analysing Peripheral Skeletal Muscle Function Before and After Endobronchial Valve Treatment
Official title: Analysing cEllular Bioenergetics aNd Structural aDaptations in the qUadriceps Muscle befoRe and After endobroNChial Valve treatmEnt
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Emphysema
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2023-09-06
Enrollment: 15
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population exists of patients with severe emphysema who undergo a bronchoscopic lung volume reduction treatment with one-way endobronchial valves.

Brief summary: Rationale: 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 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. The physiologic and structural adaptations of skeletal muscle function after EBV treatment has never been investigated before.

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, prospective clinical trial 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 population: Patients with severe emphysema who are scheduled to undergo EBV treatment.

Main study parameters/endpoints: The difference in quadriceps phosphocreatine concentration (PCr), quadriceps inorganic phosphorus concentration (Pi), and quadriceps pH at rest, during progressive exercise, and recovery rate will be measured by 31P-MRS to assess the physiological effect of EBV treatment on skeletal muscle function and its bioenergetics. Furthermore, we will perform a detailed histological and biochemical analysis of muscle fiber type composition, mitochondrial density, master regulators of muscle oxidative programming, and mitochondrial respiration before and after EBV treatment.


Eligibility criteria: Inclusion Criteria:

* Patient is scheduled for a bronchoscopic lung volume treatment using one-way endobronchial valves;
* Patient read, understood and signed the Informed Consent Form.

Exclusion Criteria:

* Inability to perform a cycle ergometry test;
* Contraindications for undergoing a magnetic resonance imaging scan (e.g. claustrophobia, implanted cardiac devices);
* Body length \>190cm;
* Any anticoagulant therapy;
* COPD exacerbation 4 weeks prior to testing.

Primary outcomes:
measure: Change in quadriceps phosphocreatine concentration measured by 31P-MRS.
timeFrame: 6 months
Secondary outcomes:
measure: Change in muscle fiber type composition measured in muscle biopsies.
timeFrame: 6 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Univeristy Medical Center Groningen
Study officials:
affiliation: UMC Groningen
name: Dirk-Jan Slebos, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: