Menthol for Dyspnea Relief in Health and COPD (MENTHODYSC)

November 17, 2025 updated by: Daniel Langer, KU Leuven

Effectiveness and Mechanisms of Menthol Inhalation for the Relief of Dyspnea in Health and COPD

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Recruiting
        • University Hospital Leuven
        • Principal Investigator:
          • Daniel Langer
        • Sub-Investigator:
          • Andreas von Leuopoldt
        • Principal Investigator:
          • Wim Janssens
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: WP 1a
Menthol inhalation during resistive loaded breathing trials in healthy participants.
Other: Menthol inhalation
300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask.
Placebo Comparator: WP 1b
Strawberry scent during resistive loaded breathing trials in healthy participants.
Other: Strawberry scent
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.
Experimental: WP 2a
Menthol inhalation during cycle exercise in healthy participants.
Other: Menthol inhalation
300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask.
Placebo Comparator: WP 2b
Strawberry scent during cycle exercise in healthy participants.
Other: Strawberry scent
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.
Experimental: WP 3a
Menthol inhalation during resting breathing in dyspneic COPD participants.
Other: Menthol inhalation
300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask.
Placebo Comparator: WP 3b
Strawberry scent during resting breathing in dyspneic COPD participants.
Other: Strawberry scent
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.
No Intervention: WP 3c
Resting breathing in dyspneic COPD participants.
Experimental: WP 4a
Menthol inhalation during cycle exercise in COPD participants.
Other: Menthol inhalation
300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask.
Placebo Comparator: WP 4b
Strawberry scent during cycle exercise in COPD participants.
Other: Strawberry scent
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.
Experimental: WP 5a
Menthol inhalation and facial airflow during cycle exercise in COPD participants
Other: Menthol inhalation and facial airflow
Menthol will be administered using a noseplug and facial airflow will be applied with a tabletop fan.
Placebo Comparator: WP 5b
Strawberry inhalation and airflow to leg during cycle exercise in COPD participants
Other: Strawberry scent and airflow to leg
Strawberry will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan.
Placebo Comparator: WP 5c
Menthol inhalation and airflow to leg during cycle exercise in COPD patients
Other: Menthol inhalation and airflow to leg
Menthol will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan.
Placebo Comparator: WP 5d
Strawberry inhalation and facial airflow during cycle exercise in COPD patients
Other: Strawberry inhalation and facial airflow
Strawberry will be administered using a noseplug and facial airflow will be applied with a tabletop fan.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
1 week

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Difference in diaphragmatic electromyography with menthol vs. strawberry.
Time Frame: 1 week
Diaphragmatic electromyography will be measured using a multi-pair electrode catheter during breathing trials and exercise tests. and used as an index of neural respiratory drive.
1 week
Difference in the cardiorespiratory responses to exercise with menthol vs. strawberry.
Time Frame: 1 week
Cardiorespiratory responses to exercise will be measured on a breath-by-breath basis using a commercially available cardiopulmonary testing system during exercise testing.
1 week
Difference in dyspnea with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5).
Time Frame: 1 week
Dyspnea ratings will be measured using the Borg 0-10 category ratio scale and will be assessed at the end of each 5-minute breathing trial (WP1 and 3), and at baseline, every minute during (WP4,5) or halfway through the test (WP2), and at peak of each cycle exercise test. 0 represents no dyspnea at all and then 10 the most maximal dyspnea ever experienced or could be imagined experiencing.
1 week
Difference in the rate of perceived inspiratory airflow.
Time Frame: 1 week
Participants will be asked: "In which of the four conditions did your airflow feel easier when breathing in?" at the end of each study visit.
1 week
Perception of a cooling sensation.
Time Frame: 1 week
Participants will be asked: "In which of the four conditions did you feel a fresh or cooling sensation when breathing in?" at the end of each study visit.
1 week
Difference in activation of extra-diaphragmatic inspiratory muscles with menthol vs. strawberry.
Time Frame: 1 week
Activation of extra-diaphragmatic inspiratory muscles will be measured using bipolar surface electrodes during breathing trials (WP3) and exercise testing (WP4).
1 week
Difference in respiratory pressures with menthol vs. strawberry.
Time Frame: 1 week
Respiratory pressures will be measured using esophageal and gastric balloons during breathing trials and exercise testing.
1 week
Difference in leg discomfort ratings with menthol vs. strawberry (+facial airflow or airflow to leg in WP5).
Time Frame: 1 week
Leg discomfort will be measured using the Borg 0-10 category ratio scale at baseline, every minute during (WP4, 5) or halfway through the test (WP2), and at peak of each cycle exercise test. 0 represents no leg discomfort at all and then 10 the most maximal leg discomfort ever experienced or could be imagined experiencing.
1 week
Difference in exercise endurance time with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5).
Time Frame: 1 week
Exercise endurance time will be measured during submaximal constant load cycle exercise testing (WP4, 5).
1 week
Difference in the reasons for stopping exercise with menthol vs. strawberry (+facial airflow or airflow to leg in WP5).
Time Frame: 1 week
Participants will be asked to give their reasons for stopping (e.g., "breathing discomfort," "leg discomfort," "a combination of breathing and leg discomfort," or "other") and attributing a percentage to each of breathing discomfort and leg discomfort to total 100 (WP 2, 4 and 5).
1 week
Difference in ratings of affective state on the dimensions of valence and arousal with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5).
Time Frame: 1 week
Dimensions of valence and arousal will be measured using the 9-point Self-Assessment Manikin scale for valence (1 -"unpleasant" to 9 -"pleasant") and arousal (1-"calm" to 9-"aroused") at the end of each breathing trial (WP 1 and 3) and at peak exercise (WP 2, 4 and 5).
1 week
Difference in the Neural Drive to Breathe (P0.1)
Time Frame: 1 week
The neural drive to breathe will be measured using airway occlusion pressure (P0.1), evoked by inspiratory occlusions delivered during the test (WP1 and 2).
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
KU Leuven

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniel Langer, KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 19, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • S66762

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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