search
Back to results

Menthol for Dyspnea Relief in Health and COPD (MENTHODYSC)

Primary Purpose

Dyspnea, Chronic Obstructive Pulmonary Disease

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Menthol inhalation
Strawberry scent
Sponsored by
KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dyspnea focused on measuring Menthol

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University Hospital LeuvenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

No Intervention

Experimental

Placebo Comparator

Arm Label

WP 1a

WP 1b

WP 2a

WP 2b

WP 3a

WP 3b

WP 3c

WP 4a

WP 4b

Arm Description

Menthol inhalation during resistive loaded breathing trials in healthy participants.

Strawberry scent during resistive loaded breathing trials in healthy participants.

Menthol inhalation during cycle exercise in healthy participants.

Strawberry scent during cycle exercise in healthy participants.

Menthol inhalation during resting breathing in dyspneic COPD participants.

Strawberry scent during resting breathing in dyspneic COPD participants.

Resting breathing in dyspneic COPD participants.

Menthol inhalation during cycle exercise in COPD participants.

Strawberry scent during cycle exercise in COPD participants.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
February 7, 2023
Last Updated
March 14, 2023
Sponsor
KU Leuven
search

1. Study Identification

Unique Protocol Identification Number
NCT05785026
Brief Title
Menthol for Dyspnea Relief in Health and COPD
Acronym
MENTHODYSC
Official Title
Effectiveness and Mechanisms of Menthol Inhalation for the Relief of Dyspnea in Health and COPD
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2023 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
June 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dyspnea, Chronic Obstructive Pulmonary Disease
Keywords
Menthol

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
WP 1a
Arm Type
Experimental
Arm Description
Menthol inhalation during resistive loaded breathing trials in healthy participants.
Arm Title
WP 1b
Arm Type
Placebo Comparator
Arm Description
Strawberry scent during resistive loaded breathing trials in healthy participants.
Arm Title
WP 2a
Arm Type
Experimental
Arm Description
Menthol inhalation during cycle exercise in healthy participants.
Arm Title
WP 2b
Arm Type
Placebo Comparator
Arm Description
Strawberry scent during cycle exercise in healthy participants.
Arm Title
WP 3a
Arm Type
Experimental
Arm Description
Menthol inhalation during resting breathing in dyspneic COPD participants.
Arm Title
WP 3b
Arm Type
Placebo Comparator
Arm Description
Strawberry scent during resting breathing in dyspneic COPD participants.
Arm Title
WP 3c
Arm Type
No Intervention
Arm Description
Resting breathing in dyspneic COPD participants.
Arm Title
WP 4a
Arm Type
Experimental
Arm Description
Menthol inhalation during cycle exercise in COPD participants.
Arm Title
WP 4b
Arm Type
Placebo Comparator
Arm Description
Strawberry scent during cycle exercise in COPD participants.
Intervention Type
Other
Intervention Name(s)
Menthol inhalation
Intervention Description
300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask.
Intervention Type
Other
Intervention Name(s)
Strawberry scent
Intervention Description
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.
Primary Outcome Measure Information:
Title
Difference in respiratory-related evoked potentials (RREP) with menthol vs. strawberry.
Description
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.
Time Frame
1 week
Other Pre-specified Outcome Measures:
Title
Difference in diaphragmatic electromyography with menthol vs. strawberry.
Description
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.
Time Frame
1 week
Title
Difference in dyspnea with menthol vs. strawberry.
Description
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 minutes during, and at peak of each cycle exercise test (WP2 and 4). 0 represents no dyspnea at all and then 10 the most maximal dyspnea ever experienced or could be imagined experiencing.
Time Frame
1 week
Title
Difference in the rate of perceived inspiratory airflow
Description
Participants will be asked: "In which of the two conditions did your airflow feel easier when breathing in?" at the end of each study visit.
Time Frame
1 week
Title
Perception of a cooling sensation
Description
Participants will be asked: "In which of the two conditions did you feel a fresh or cooling sensation when breathing in?" at the end of each study visit.
Time Frame
1 week
Title
Difference in activation of extra-diaphragmatic inspiratory muscles with menthol vs. strawberry.
Description
Activation of extra-diaphragmatic inspiratory muscles will be measured using bipolar surface electrodes during breathing trials and exercise testing.
Time Frame
1 week
Title
Difference in the cardiorespiratory responses to exercise with menthol vs. strawberry.
Description
Cardiorespiratory responses to exercise will be measured on a breath-by-breath basis using a commercially available cardiopulmonary testing system during exercise testing.
Time Frame
1 week
Title
Difference in respiratory pressures with menthol vs. strawberry
Description
Respiratory pressures will be measured using esophageal and gastric balloons during breathing trials and exercise testing.
Time Frame
1 week
Title
Difference in leg discomfort ratings with menthol vs. strawberry.
Description
Leg discomfort will be measured using the Borg 0-10 category ratio scale at baseline, every minute during, and at peak of each cycle exercise test (WP2 and 4). 0 represents no leg discomfort at all and then 10 the most maximal leg discomfort ever experienced or could be imagined experiencing.
Time Frame
1 week
Title
Difference in exercise endurance time with menthol vs. strawberry.
Description
Exercise endurance time will be measured during submaximal constant load cycle exercise testing (WP 2 and 4).
Time Frame
1 week
Title
Difference in the reasons for stopping exercise with menthol vs. strawberry.
Description
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 and 4).
Time Frame
1 week
Title
Difference in ratings of affective state on the dimensions of valence and arousal with menthol vs. strawberry.
Description
Dimensions of valence and arousal will be measured using the 9-point SAM scale at the end of each breathing trial (WP 1 and 3) and at peak exercise (WP 2 and 4).
Time Frame
1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Langer
Phone
+32 16 37 64 97
Email
daniel.langer@kuleuven.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Langer
Organizational Affiliation
KU Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Langer
Email
daniel.langer@kuleuven.be
First Name & Middle Initial & Last Name & Degree
Daniel Langer
First Name & Middle Initial & Last Name & Degree
Andreas von Leuopoldt
First Name & Middle Initial & Last Name & Degree
Wim Janssens

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Menthol for Dyspnea Relief in Health and COPD

We'll reach out to this number within 24 hrs