Menthol for Dyspnea Relief in Health and COPD

Not Applicable

Recruiting

• Conditions: Chronic Obstructive Pulmonary Disease; Dyspnea
• Interventions: Other: Menthol inhalation; Other: Strawberry scent

• Registration Number: NCT05785026
• Lead Sponsor: KU Leuven

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).

Study Timeline

• Study Start: 2023-01-01
• Study First Submitted: 2023-02-07
• Study First Submitted QC: 2023-03-14
• Study First Posted: 2023-03-27
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-05
• Last Update Posted: 2024-06-06
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
WP 4a	Menthol inhalation	Menthol inhalation during cycle exercise in COPD participants.
WP 1b	Strawberry scent	Strawberry scent during resistive loaded breathing trials in healthy participants.
WP 2a	Menthol inhalation	Menthol inhalation during cycle exercise in healthy participants.
WP 3a	Menthol inhalation	Menthol inhalation during resting breathing in dyspneic COPD participants.
WP 3b	Strawberry scent	Strawberry scent during resting breathing in dyspneic COPD participants.
WP 1a	Menthol inhalation	Menthol inhalation during resistive loaded breathing trials in healthy participants.
WP 2b	Strawberry scent	Strawberry scent during cycle exercise in healthy participants.
WP 4b	Strawberry scent	Strawberry scent during cycle exercise in COPD participants.

Primary Outcome Measures

Name	Time	Method
Difference in respiratory-related evoked potentials (RREP) with menthol vs. strawberry.	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.

Trial Locations

Locations (1)

University Hospital Leuven; 🇧🇪 Leuven, Belgium