Inhaled Nebulized Furosemide & Physical Activity-Related Breathlessness

Study Overview
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Brief Summary
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Breathlessness on exertion is a common and troublesome complaint of individuals with restrictive lung disorders. In these adults, breathlessness contributes to physical activity-limitation and avoidance and an adverse health-related quality-of-life, often in a self-perpetuating cycle. It follows that alleviating dyspnea and improving exercise tolerance are among the principal goals in the management of adults with restrictive lung disorders. Nevertheless, effective management of breathlessness and physical activity-limitation remains an elusive goal for many healthcare providers and current therapies (e.g., antifibrotic agents, oxygen, exercise training) are only partially successful in this regard. Thus, research aimed at identifying breathlessness-specific medications to complement existing therapies for the management of physical activity-related breathlessness in restrictive lung disorders is timely and both clinically and physiologically relevant. The purpose of this randomized crossover study study is to examine the acute effects of two doses of inhaled nebulized furosemide (a loop diuretic) on the perception of breathlessness during laboratory-based cycle exercise in healthy, young men in the presence of an external thoracic restriction to mimic a 'mild' restrictive lung deficit. To this end, the investigators will compare the effects of inhaled 0.9% saline placebo and inhaled furosemide (40 mg and 120 mg) on detailed assessments of breathlessness (sensory intensity and affective responses) and its physiological determinants (ventilation, breathing pattern, dynamic operating lung volumes, cardio-metabolic function) symptom-limited, high-intensity, constant-work-rate cycle exercise testing with external thoracic restriction sufficient to mimic a 'mild' restrictive pulmonary deficit in healthy, men aged 18-40 years.

Official Title
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Effects of Inhaled Furosemide on Breathlessness During Exercise in the Presence of External Thoracic Restriction: A Dose-Reponse Study

Conditions
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Breathlessness

Intervention / Treatment
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* Other: CWS
* Drug: Furosemide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Aged 18-40 years FEV1 ≥80% predicted FEV1/FVC >70% Exclusion Criteria: Current or ex-smoker Body Mass Index <18.5 or >30 kg/m2 Self-reported history of cardiovascular, vascular, respiratory, renal, liver, musculoskeletal, endocrine, neuromuscular and/or metabolic disease/dysfunction Taking doctor prescribed medications Allergy to sulfa medications

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CWS+Furosemide (40 mg)<br>Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of furosemide (40 mg) | Other: CWS<br>* Chest wall strapping to reduced vital capacity by 20% of its baseline value<br>* Other names: Chest wall strapping;Drug: Furosemide<br>* 40 mg and 120 mg<br>|
| Placebo Comparator: CWS+0.9% saline placebo<br>Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of 0.9% saline placebo | Other: CWS<br>* Chest wall strapping to reduced vital capacity by 20% of its baseline value<br>* Other names: Chest wall strapping;Drug: Placebo<br>* 0.9% saline<br>|
| Experimental: CWS+Furosemide (120 mg)<br>Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of furosemide (120 mg) | Other: CWS<br>* Chest wall strapping to reduced vital capacity by 20% of its baseline value<br>* Other names: Chest wall strapping;Drug: Furosemide<br>* 40 mg and 120 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensory intensity (Borg 0-10 scale) ratings of dyspnea at isotime |  | Participants will be followed until all study visits are completed, an expected average of 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Furosemide, Exercise, Restrictive pulmonary disorder