Effectiveness and Mechanisms of Menthol Inhalation for the Relief of Dyspnea in Health and COPD
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- KU Leuven
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Difference in respiratory-related evoked potentials (RREP) with menthol vs. strawberry.
Study Overview
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 5 work packages (WP), each including a different sample of healthy volunteers (WP1, 2) or patients with COPD (WP3, 4, 5), 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, 5).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
WP 3c
Resting breathing in dyspneic COPD participants.
WP 4a
Menthol inhalation during cycle exercise in COPD participants.
Intervention: Menthol inhalation (Other)
WP 4b
Strawberry scent during cycle exercise in COPD participants.
Intervention: Strawberry scent (Other)
WP 1a
Menthol inhalation during resistive loaded breathing trials in healthy participants.
Intervention: Menthol inhalation (Other)
WP 1b
Strawberry scent during resistive loaded breathing trials in healthy participants.
Intervention: Strawberry scent (Other)
WP 2a
Menthol inhalation during cycle exercise in healthy participants.
Intervention: Menthol inhalation (Other)
WP 2b
Strawberry scent during cycle exercise in healthy participants.
Intervention: Strawberry scent (Other)
WP 3a
Menthol inhalation during resting breathing in dyspneic COPD participants.
Intervention: Menthol inhalation (Other)
WP 3b
Strawberry scent during resting breathing in dyspneic COPD participants.
Intervention: Strawberry scent (Other)
WP 5a
Menthol inhalation and facial airflow during cycle exercise in COPD participants
Intervention: Menthol inhalation and facial airflow (Other)
WP 5b
Strawberry inhalation and airflow to leg during cycle exercise in COPD participants
Intervention: Strawberry scent and airflow to leg (Other)
WP 5c
Menthol inhalation and airflow to leg during cycle exercise in COPD patients
Intervention: Menthol inhalation and airflow to leg (Other)
WP 5d
Strawberry inhalation and facial airflow during cycle exercise in COPD patients
Intervention: Strawberry inhalation and facial airflow (Other)
Outcomes
Primary Outcomes
Difference in respiratory-related evoked potentials (RREP) with menthol vs. strawberry.
Time Frame: 1 week
RREPs will be measured using an electroencephalogram (EEG) sensor cap connected to a high-density 129 channel EEG system during breathing trials and exercise tests. Inspiration will briefly be interrupted for 150 milliseconds every two to six breaths by activation of the occluder, which induces the RREP in the EEG signal.
Secondary Outcomes
No secondary outcomes reported
Investigators
Daniel Langer
Assistant Professor
KU Leuven