Aerosol Particle Size and Breathing Pattern During Inhaled Furosemide (FurAH-II)

Effect of Aerosol Particle Size and Breathing Pattern of Inhalation on Relief of Experimentally Induced Air Hunger by Inhaled Furosemide

The study hypothesises that the variability in relief of air hunger with inhaled furosemide that is reported in previous studies can be explained by the breathing pattern adopted during the inhalation and the droplet size in the aerosol, both of which would influence the site of deposition of the aerosol in the lungs

Study Overview

• Status: Unknown
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Inhaled furosemide

Detailed Description

Recent studies suggest that inhaling furosemide as a mist reduces air hunger in healthy volunteers in whom air hunger is induced experimentally in the lab. However, how much reduction varies among individuals. It is not known if the way the mist is breathed (slow/deep or fast/shallow) or the size of the droplets in the mist (large or small) can explain the variation in relief. Both of these factors can influence the site of deposition of the aerosol in the lungs

In this study the relief of air hunger (induced by hypercapnia and constrained ventilation) will be compared when furosemide is inhaled quickly or slowly, and when the mist has large or small droplets. 20 healthy volunteers will be recruited. After a practice session, the 'air hunger' test will be performed before and after 4ml of a 10mg/ml solution of furosemide (40mg). This will be repeated on 4 separate test days using a different method of inhaling the furosemide on each day.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 0BP
      • Recruiting
      • Oxford Brookes University
      • Contact: Shakeeb H Moosavi, PhD; Phone Number: 3257 +44 (0)1865 4823257; Email: smoosavi@brookes.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Healthy volunteers aged 18 and over

Exclusion Criteria:

• On any medication, including herbal medication (other than mild analgesics, vitamins and mineral supplements or, for females, oral contraceptives), whether prescribed or over-the-counter, in the two weeks prior to test sessions involving administration of furosemide or saline.
• Female participants who are pregnant, lactating or planning pregnancy over the course of trial
• A medical history of heart, kidney or liver disease/electrolyte disturbances/ immunosuppression/frequent fainting episodes/COPD/nasal polyps/Addison's/acute porphyria/significant prostatic symptoms/acute gout attack/life expectancy <6months or history of allergic reaction to furosemide and/or any of the other ingredients of furosemide or amiloride, sulfonamides or sulphonamide derivatives, such as sulfadiazine or co-trimoxazole
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
• Have participated in another research trial involving an investigational product in the past 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Slow/Deep/Large; Slow/deep breathing pattern will be targeted while inhaling furosemide with nebulizer set to deliver 4ml of a 10mg/ml solution of furosemide with large droplet size over a 10-15 minute duration	Drug: Inhaled furosemide; 4ml of 10mg/ml solution of furosemide nebulized with small and large droplet sizes and inhaled with different breathing patterns; Other Names: Lasix
Active Comparator: Slow/Deep/Small; Slow/deep breathing pattern will be targeted while inhaling furosemide with nebulizer set to deliver 4ml of a 10mg/ml solution of furosemide with small droplet size over a 10-15 minute duration.	Drug: Inhaled furosemide; 4ml of 10mg/ml solution of furosemide nebulized with small and large droplet sizes and inhaled with different breathing patterns; Other Names: Lasix
Active Comparator: Fast/Shallow/Large; Fast/shallow breathing pattern will be targeted while inhaling furosemide with nebulizer set to deliver 4ml of a 10mg/ml solution of furosemide with large droplet size over a 10-15 minute duration.	Drug: Inhaled furosemide; 4ml of 10mg/ml solution of furosemide nebulized with small and large droplet sizes and inhaled with different breathing patterns; Other Names: Lasix
Active Comparator: Fast/Shallow/Small; Fast/shallow breathing pattern will be targeted while inhaling furosemide with nebulizer set to deliver 4ml of a 10mg/ml solution of furosemide with small droplet size over a 10-15 minute duration.	Drug: Inhaled furosemide; 4ml of 10mg/ml solution of furosemide nebulized with small and large droplet sizes and inhaled with different breathing patterns; Other Names: Lasix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual analogue scale for air hunger	The visual analogue scale (VAS) is from 0 (no air hunger) to 100 (extreme air hunger -tolerable limit). The VAS ratings are taken every 15 seconds during each experimentally induced air hunger test. Each breathing test (hypercapnia with constrained ventilation) is performed before and after each mist inhalation. The final minute of a 5 minute steady state period of hypercapnia and constrained ventilation is analysed during each breathing test (8 breathing tests in total)	Final minute of a 5 minute steady state period per breathing test

Collaborators and Investigators

• Sponsor: Oxford Brookes University

Publications and helpful links

General Publications

• Grogono JC, Butler C, Izadi H, Moosavi SH. Inhaled furosemide for relief of air hunger versus sense of breathing effort: a randomized controlled trial. Respir Res. 2018 Sep 20;19(1):181. doi: 10.1186/s12931-018-0886-9.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2019
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: October 16, 2019
• First Submitted That Met QC Criteria: October 16, 2019
• First Posted (Actual): October 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2019
• Last Update Submitted That Met QC Criteria: October 16, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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: L19185

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