Inhaled Nebulized Furosemide & Physical Activity-Related Breathlessness

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

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.

Study Overview

• Status: Unknown
• Conditions: Breathlessness
• Intervention / Treatment: Drug: Placebo; Other: CWS; Drug: Furosemide

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Centre of Innovative Medicine of the McGill University Health Centre
      • Contact: Dennis Jensen, Ph.D.; Phone Number: 0472 514-398-4184; Email: dennis.jensen@mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CWS+Furosemide (40 mg); Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of furosemide (40 mg)	Other: CWS; Chest wall strapping to reduced vital capacity by 20% of its baseline value; Other Names: Chest wall strapping; Drug: Furosemide; 40 mg and 120 mg
PLACEBO_COMPARATOR: CWS+0.9% saline placebo; Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of 0.9% saline placebo	Drug: Placebo; 0.9% saline; Other: CWS; Chest wall strapping to reduced vital capacity by 20% of its baseline value; Other Names: Chest wall strapping
EXPERIMENTAL: CWS+Furosemide (120 mg); Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of furosemide (120 mg)	Other: CWS; Chest wall strapping to reduced vital capacity by 20% of its baseline value; Other Names: Chest wall strapping; Drug: Furosemide; 40 mg and 120 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: McGill University

Publications and helpful links

Helpful Links

• Clinical Exercise & Respiratory Physiology Laboratory (CERPL) of McGill University

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (ANTICIPATED): April 1, 2017
• Study Completion (ANTICIPATED): September 1, 2017

Study Registration Dates

• First Submitted: May 7, 2013
• First Submitted That Met QC Criteria: May 10, 2013
• First Posted (ESTIMATE): May 13, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Exercise; Furosemide; Restrictive pulmonary disorder
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Dyspnea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 15-370-MUHC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO