NCT05785026

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for not_applicable

Timeline
30mo left

Started Jan 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress57%
Jan 2023Oct 2028

Study Start

First participant enrolled

January 1, 2023

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

February 7, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

March 27, 2023

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2028

Last Updated

November 19, 2025

Status Verified

November 1, 2025

Enrollment Period

5.8 years

First QC Date

February 7, 2023

Last Update Submit

November 17, 2025

Conditions

Keywords

Menthol

Outcome Measures

Primary Outcomes (1)

  • Difference in respiratory-related evoked potentials (RREP) with menthol vs. strawberry.

    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.

    1 week

Other Outcomes (12)

  • Difference in diaphragmatic electromyography with menthol vs. strawberry.

    1 week

  • Difference in dyspnea with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5).

    1 week

  • Difference in the rate of perceived inspiratory airflow.

    1 week

  • +9 more other outcomes

Study Arms (13)

WP 1a

EXPERIMENTAL

Menthol inhalation during resistive loaded breathing trials in healthy participants.

Other: Menthol inhalation

WP 1b

PLACEBO COMPARATOR

Strawberry scent during resistive loaded breathing trials in healthy participants.

Other: Strawberry scent

WP 2a

EXPERIMENTAL

Menthol inhalation during cycle exercise in healthy participants.

Other: Menthol inhalation

WP 2b

PLACEBO COMPARATOR

Strawberry scent during cycle exercise in healthy participants.

Other: Strawberry scent

WP 3a

EXPERIMENTAL

Menthol inhalation during resting breathing in dyspneic COPD participants.

Other: Menthol inhalation

WP 3b

PLACEBO COMPARATOR

Strawberry scent during resting breathing in dyspneic COPD participants.

Other: Strawberry scent

WP 3c

NO INTERVENTION

Resting breathing in dyspneic COPD participants.

WP 4a

EXPERIMENTAL

Menthol inhalation during cycle exercise in COPD participants.

Other: Menthol inhalation

WP 4b

PLACEBO COMPARATOR

Strawberry scent during cycle exercise in COPD participants.

Other: Strawberry scent

WP 5a

EXPERIMENTAL

Menthol inhalation and facial airflow during cycle exercise in COPD participants

Other: Menthol inhalation and facial airflow

WP 5b

PLACEBO COMPARATOR

Strawberry inhalation and airflow to leg during cycle exercise in COPD participants

Other: Strawberry scent and airflow to leg

WP 5c

PLACEBO COMPARATOR

Menthol inhalation and airflow to leg during cycle exercise in COPD patients

Other: Menthol inhalation and airflow to leg

WP 5d

PLACEBO COMPARATOR

Strawberry inhalation and facial airflow during cycle exercise in COPD patients

Other: Strawberry inhalation and facial airflow

Interventions

300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask.

WP 1aWP 2aWP 3aWP 4a

600 microliters of 100% natural strawberry flavoring will be deposited onto on to a cellulose swab and secured inside the lower portion of a sealed facemask.

WP 1bWP 2bWP 3bWP 4b

Menthol will be administered using a noseplug and facial airflow will be applied with a tabletop fan.

WP 5a

Strawberry will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan.

WP 5b

Menthol will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan.

WP 5c

Strawberry will be administered using a noseplug and facial airflow will be applied with a tabletop fan.

WP 5d

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Leuven

Leuven, 3000, Belgium

RECRUITING

Related Publications (1)

  • Schaeffer MR, Vanden Bossche L, Beckers K, Verbeke K, Janssens W, Jensen D, Arnold JI, von Leupoldt A, Langer D. Inhaled Menthol for Dyspnea Relief During Cycle Exercise in COPD: A Randomized Trial. Chest. 2025 Aug;168(2):390-401. doi: 10.1016/j.chest.2025.03.002. Epub 2025 Mar 13.

MeSH Terms

Conditions

DyspneaPulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Respiration DisordersRespiratory Tract DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsLung Diseases, ObstructiveLung DiseasesChronic DiseaseDisease AttributesPathologic Processes

Study Officials

  • Daniel Langer

    KU Leuven

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

February 7, 2023

First Posted

March 27, 2023

Study Start

January 1, 2023

Primary Completion (Estimated)

October 31, 2028

Study Completion (Estimated)

October 31, 2028

Last Updated

November 19, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will not share

Locations