Efficacy of L-menthol on Breathlessness in Chronic Obstructive Pulmonary Disease (Ment-COPD)

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: L-menthol; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden
    • Lund University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Menthol; 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; (Sigma-Aldrich, St. Louis, US)
Placebo Comparator: Placebo; For placebo, the patch will contain a similarly patch with strawberry scent.	Other: Placebo; Strawberry scent (Sigma-Aldrich, St. Louis, US)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: Lund University
• Investigators: Principal Investigator: Zainab Ahmadi, MD, PhD, Region Skane

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): June 5, 2023

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Organic Chemicals; Lipids; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Alcohols; Cyclohexanols; Hexanols; Fatty Alcohols; Cyclohexane Monoterpenes; Monoterpenes; Menthol
• Other Study ID Numbers: Ment-COPD

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