Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| WP 1a | Experimental | Menthol inhalation during resistive loaded breathing trials in healthy participants. |
|
| WP 1b | Placebo Comparator | Strawberry scent during resistive loaded breathing trials in healthy participants. |
|
| WP 2a | Experimental | Menthol inhalation during cycle exercise in healthy participants. |
|
| WP 2b | Placebo Comparator | Strawberry scent during cycle exercise in healthy participants. |
|
| WP 3a | Experimental | Menthol inhalation during resting breathing in dyspneic COPD participants. |
|
| WP 3b | Placebo Comparator | Strawberry scent during resting breathing in dyspneic COPD participants. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Menthol inhalation | Other | 300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Difference in diaphragmatic electromyography with menthol vs. strawberry. | 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 dyspnea with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5). |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daniel Langer | Contact | +32 16 37 64 97 | daniel.langer@kuleuven.be |
| Name | Affiliation | Role |
|---|---|---|
| Daniel Langer | KU Leuven | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Leuven | Recruiting | Leuven | 3000 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40088943 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D004417 | Dyspnea |
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| WP 3c | No Intervention | Resting breathing in dyspneic COPD participants. |
| WP 4a | Experimental | Menthol inhalation during cycle exercise in COPD participants. |
|
| WP 4b | Placebo Comparator | Strawberry scent during cycle exercise in COPD participants. |
|
| WP 5a | Experimental | Menthol inhalation and facial airflow during cycle exercise in COPD participants |
|
| WP 5b | Placebo Comparator | Strawberry inhalation and airflow to leg during cycle exercise in COPD participants |
|
| WP 5c | Placebo Comparator | Menthol inhalation and airflow to leg during cycle exercise in COPD patients |
|
| WP 5d | Placebo Comparator | Strawberry inhalation and facial airflow during cycle exercise in COPD patients |
|
| Strawberry scent | Other | 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. |
|
| Menthol inhalation and facial airflow | Other | Menthol will be administered using a noseplug and facial airflow will be applied with a tabletop fan. |
|
| Strawberry scent and airflow to leg | Other | Strawberry will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan. |
|
| Menthol inhalation and airflow to leg | Other | Menthol will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan. |
|
| Strawberry inhalation and facial airflow | Other | Strawberry will be administered using a noseplug and facial airflow will be applied with a tabletop fan. |
|
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. | 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. | 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. | 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 the cardiorespiratory responses to exercise with menthol vs. strawberry. | 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 respiratory pressures with menthol vs. strawberry. | 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). | 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). | 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). | 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). | 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) | 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 |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |