Efficacy of L-menthol on Breathlessness in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of L-menthol on breathlessness in patients with chronic obstructive pulmonary disease (COPD).

Detailed Description
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Breathelssness (Dyspnea) is a cardinal symptom in patients with chronic obstructive pulmonary disease (COPD), often triggered by daily-life physical activities. Despite optimal treatment of the underlying disease, many patients still suffer from chronic and disabling dyspnea for many years, leading to exercise intolerance, and worse morbidity and mortality. To date, an effective pharmacologic treatment to relieve chronic dyspnea is lacking. Recent pilot data support that inhaled L-menthol can markedly decrease laboratory-induced dyspnea in COPD patients, likely through increased afferent feedback of airflow in the airways by inducing a cooling sensation through olfactory stimulation. The aim of this study is therefore to assess the effectiveness and mechanisms of inhaled menthol for relief of chronic dyspnea in patients with COPD.

Official Title
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Effect of L-menthol on Breathlessness and Exercise Capacity in Chronic Obstructive Pulmonary Disease: a Randomized

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: L-menthol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has given written consent to participate in the study Diagnosis of COPD confirmed by spirometry and a FEV1 < 80% of predicted post bronchodilator at baseline age 18 years or older able to cycle able to understand and talk Swedish to participate in the study procedures, as judged by the Investigator. Exclusion Criteria: Resting peripheral oxygen saturation (SpO2) < 92% hospitalization or clinical instability during the last four weeks treatment with supplementary oxygen at rest or during exercise contraindication to exercise testing in accordance with clinical practice guidelines expected survival shorter than six months as judged by the Investigator medical conditions including congestive heart failure, acute coronary artery disease, neuromuscular diseases, severe psychiatric illness, and olfaction disorder.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-center, randomized (ratio 1:1), double-blinded, placebo-controlled, crossover trial (RCT) design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menthol<br>In the trial, 30 minutes prior to performing submaximal CPET, participants will be administered, L-menthol patch which will be attached to the inside of a facemask that is connected to the breathing circuit. | Drug: L-menthol<br>* (Sigma-Aldrich, St. Louis, US)<br>|
| Placebo Comparator: Placebo<br>For placebo, the patch will contain a similarly patch with strawberry scent. | Other: Placebo<br>* Strawberry scent (Sigma-Aldrich, St. Louis, US)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breathlessness intensity | The difference between treatment conditions in dyspnea intensity (Borg CR10 scale) at iso-time. | Through study completion, up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea unpleasantness | The difference between treatment conditions in dyspnea unpleasantness (Borg CR10 scale) at iso-time. | Through study completion, up to 1 year | 
| Total time | Time to the limit of tolerance (s) (tLIM) | Through study completion, up to 1 year | 
| Exercise capacity | V'O2 (aerobic exercise capacity, absolute and in %pred) | Through study completion, up to 1 year | 
| Work load | Workload (W and %pred) | Through study completion, up to 1 year | 
| Minute ventilation | Minute ventilation | Through study completion, up to 1 year | 
| Tidal volume (VT) | Tidal volume (VT) | Through study completion, up to 1 year | 
| Ventilatory reserve | Ventilatory reserve, defined as maximal voluntary ventilation (MVV) - VE | Through study completion, up to 1 year | 
| Cardiac reserve | Cardiac reserve, evaluated using the predicted peak heart rate | Through study completion, up to 1 year | 
| Inspiratory capacity | Inspiratory capacity (IC) during exercise | Through study completion, up to 1 year | 
| Breathing frequency | Breathing frequency during exercise | Through study completion, up to 1 year | 
| Peak dyspnea intensity | Dyspnea intensity at peak exercise (Borg CR10) | Through study completion, up to 1 year | 
| Leg discomfort | Leg discomfort (Borg CR10) | Through study completion, up to 1 year | 
| Anaerobic threshold | Timing (and V'O2) of the anaerobic threshold (AT) | Through study completion, up to 1 year | 
| Ventilatory efficacy | Efficacy of ventilation (VE/V'CO2-slope) | Through study completion, up to 1 year | 
| Respiratory exchange ratio | Respiratory exchange ratio (RER), defined as V'CO2/V'O2 | Through study completion, up to 1 year | 
| Saturation | O2-saturation | Through study completion, up to 1 year | 
| Stop reason | Causes of stopping the test | Through study completion, up to 1 year | 
| Adverse events | Any adverse events during the test | Through study completion, up to 1 year |