Clinical trial NCT05785026: Menthol for Dyspnea Relief in Health and COPD
Official title: Effectiveness and Mechanisms of Menthol Inhalation for the Relief of Dyspnea in Health and COPD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dyspnea
Chronic Obstructive Pulmonary Disease
Keywords: Menthol
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2023-03-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Menthol inhalation (MI) is a novel and promising treatment option for acute relief of dyspnea, however, the underlying ventilatory and/or neural related mechanisms for this relief in symptoms remain unknown. The overall aim of this research project is to systematically examine the mechanisms of dyspnea relief from MI in healthy individuals and those with COPD.

Detailed description: The project is structured in 4 work packages (WP), each including a different sample of healthy volunteers (WP1, 2) or patients with COPD (WP3, 4), respectively with a 1:1 female/male ratio in each WP. Each WP will be single-blind, placebo-controlled cross-over trial to investigate the effects of MI compared to placebo in healthy volunteers during resistive loaded breathing (WP1), in healthy volunteers during cycling exercise (WP2), in people with COPD who have dyspnea at rest (WP3), and in people with COPD during cycling exercise (WP4).

Eligibility criteria: Inclusion Criteria:

* Age: 18 years of age or older
* Able to speak, read, and write Dutch or English
* Normal pulmonary function: forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio\>0.70; FEV1≥80%predicted (WP1 and 2 only)
* Non-smoker or former smokers (smoke-free ≥12 months prior to enrolment) (WP1 and 2 only)
* Clinically stable COPD (based on clinical judgment of the study physician that have not had exacerbations requiring escalation of medical therapy (i.e., short course of oral corticosteroids or antibiotics) within the preceding 14 days (WP3 and 4 only)

Exclusion Criteria:

* Contraindication to exercise testing (e.g., significant cardiovascular, musculoskeletal, neurological disease; see Table 4 from ERS/ATS consensus statement)
* Significant pulmonary or extra-pulmonary disease that, based on clinical assessment, could influence dyspnea and/or impair exercise capacity (with the exception of COPD in WP3 and 4)
* Body mass index \<18.5 or \>35 kg/m2
* An ulcer or tumor in the esophagus, a nasal septum deviation, or recent nasopharyngeal surgery
* Severe facial trauma including cribriform plate disruption (bone separating brain from nasal cavity)
* Allergies to latex and sensitivities to local anesthetics
* Inability to give informed consent, including those with significant cognitive impairment
* Alcohol consumption within 12 hours of study visit
* Current smoker\*
* History of early menopause (age \<45 years)
* Pregnancy or desire to become pregnant while in trial

Primary outcomes:
measure: Difference in respiratory-related evoked potentials (RREP) with menthol vs. strawberry.
timeFrame: 1 week
Secondary outcomes:
Other outcomes:
measure: Difference in diaphragmatic electromyography with menthol vs. strawberry.
timeFrame: 1 week
measure: Difference in dyspnea with menthol vs. strawberry.
timeFrame: 1 week
measure: Difference in the rate of perceived inspiratory airflow
timeFrame: 1 week
measure: Perception of a cooling sensation
timeFrame: 1 week
measure: Difference in activation of extra-diaphragmatic inspiratory muscles with menthol vs. strawberry.
timeFrame: 1 week
measure: Difference in the cardiorespiratory responses to exercise with menthol vs. strawberry.
timeFrame: 1 week
measure: Difference in respiratory pressures with menthol vs. strawberry
timeFrame: 1 week
measure: Difference in leg discomfort ratings with menthol vs. strawberry.
timeFrame: 1 week
measure: Difference in exercise endurance time with menthol vs. strawberry.
timeFrame: 1 week
measure: Difference in the reasons for stopping exercise with menthol vs. strawberry.
timeFrame: 1 week
measure: Difference in ratings of affective state on the dimensions of valence and arousal with menthol vs. strawberry.
timeFrame: 1 week
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven
Study officials:
affiliation: KU Leuven
name: Daniel Langer
role: PRINCIPAL_INVESTIGATOR
References: