Inhaled Dose Analysis Using a Breath Actuated Nebulizer in Healthy Subjects

February 5, 2024 updated by: Hui-Ling Lin, Chang Gung University

The goal of this crossover study is to compare urine drug concentrations using a continuous vibrating mesh nebulizer versus a breath-actuated vibrating mesh nebulizer in healthy volunteers. The main questions it aims to answer are:

  • Whether breath-actuation nebulizer delivers higher inhaled drug dose, resulting in higher urine drug concentrations compared to continuous nebulization.
  • Whether the different nebulizer modes deliver inhaled drug resulting in different effects on physiological parameters, including heart rate, respiratory rate, blood pressure, and blood oxygen saturation.

Participants will

  • Inhale one dose (2.5mg) of salbutamol via continuous vs. breath-actuated nebulize mode.
  • collect urine samples at multiple timepoints before and after nebulization to quantify drug elimination.

Researchers will compare the continuous and breath-actuated modes of vibrating mesh nebulizers to determine if breath-actuation improves drug delivery efficiency compared to continuous nebulization.

Study Overview

Detailed Description

Study Design and Objectives

This is a crossover study comparing two different nebulizer modes: continuous vibrating mesh nebulizer (cVMN, Microbase Inc.) vs. breath-actuated vibrating mesh nebulizer (bVMN, Microbase plus an actuated system) for bronchodilator delivery in 30 healthy volunteers. The primary objective is to compare urinary drug concentrations after inhalation between the two nebulizer modes to confirm an equivalent inhaled dose. Secondary objectives is to evaluate device safety based on vital sign changes and compare environmental drug particle concentrations between nebulizer modes.

Endpoints

The primary pharmacokinetic endpoint is urinary drug (salbutamol) concentration over 24 hours following nebulization with each mode. Secondary endpoints include pre- and post-nebulization vital signs (heart rate, blood pressure, respiratory rate, Saturation).

Study Procedures

Participants meeting the eligibility criteria will be assigned either to the continuous vibrating mesh nebulizer (cVMN) or the breath-actuated vibrating mesh nebulizer (bVMN). At visit 1, a baseline urine sample will be collected, followed by nebulization with a 0.5-unit dose (2.5 mg/1.25 mL salbutamol). Participants will inhale with normal tidal breathing for up to 5 minutes until the aerosol is visually seen. Vital signs will be continuously monitored every 5 minutes until 30 minutes after nebulization. Environmental particle concentration will be continuously measured by an aerosol spectrometer. Urine samples will be obtained 30 minutes before, 30 minutes after, and 24 hours post-nebulization. Visit 2 will follow identical procedures with the alternate nebulizer mode after a 1-week washout period.

Device Details

The cVMN is a commercially available continuous vibrating mesh nebulizer registered with the Taiwan Food and Drug Administration (device number 004561). The bVMN system incorporates a proprietary trigger module to enable breath-actuated delivery synchronized during inspiration. This module includes microphone detection during inspiration and expiration phases, along with software control of nebulization activation. Both devices utilize the same core nebulizer hardware and mesh component for aerosol generation.

Data Collection and Statistics

Urine samples will be extracted and analysis by HPLC to quantify salbutamol levels. Statistical analysis will include paired t-tests or nonparametric tests as appropriate to compare pharmacokinetic parameters, environmental concentrations, and vital signs changes between the two nebulize modes. Linear regression will also correlate urinary drug levels with nominal dose. The level of significance will be p<0.05.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Taoyuan, Taiwan, 33305
        • Recruiting
        • Linkou Chang Gung Memorial Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Willing to sign a written informed consent form.
  • Healthy male and female participants aged >20 years.
  • Forced expiratory volume in the first second (FEV1) greater than 80% of the predicted value.

Exclusion Criteria:

  • Pregnant or lactating women.
  • Regular use of bronchodilators or inhaled medications.
  • History of bronchodilator allergy.
  • Hyperthyroidism.
  • Diabetes.
  • History of heart disease.
  • Arrhythmia.
  • Angina.
  • Hypertension.
  • History of glaucoma, hypokalemia, or hyperglycemia.
  • Severe anemia.
  • Individuals with severe injuries or burns or limb amputation after breast surgery.
  • Open wounds or infectious dermatitis on the oral and facial regions.
  • Acute or infectious respiratory tract infections.
  • Currently taking any medications.
  • Respiratory therapy students.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Device Feasibility
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: continuous vibrating mesh nebulization (cVMN)
Participants will inhale 2.5 mg salbutamol (from a 0.5 unit dose vial of Saldolin Inhalation Solution, Taiwan FDA approval number 043572) via the commercially available vibrating mesh nebulizer (Microbase, model number MBPN002). The device continuously generates aerosol throughout the respiratory cycle. Participants are encouraged to breathe with normal tidal breathing for up to 5 minutes until no aerosol is visually seen. No repeat or additional dosing is utilized.
When the continuous vibrating mesh nebulizer powered on, the micro-pump chip provides sustained vibrations onto the aperture plate, forcing fluid through micron-scale pores under pressure to continuously produce aerosol throughout inspiration and expiration phase.
Other Names:
  • Microbase, Model Number MBPN002
Experimental: Breath-actuated vibrating mesh nebulizer (bVMN)
Participants will inhale 2.5 mg salbutamol (from a 0.5 unit dose vial of Saldolin Inhalation Solution, Taiwan FDA approval number 043572) via the commercially available vibrating mesh nebulizer (Microbase, model number MBPN002) with trigger module attachment. This device utilizes a microphone and algorithm to detect the inspiration to activate aerosol generation during period of inspiration only. Participants are encouraged to breathe with normal tidal breathing for up to 5 minutes until no aerosol is visually seen. No repeat or additional dosing is utilized.
The intervention utilizes a breath-actuated vibrating mesh nebulizer system consisting of a controller module with microphone for respiratory phase detection and algorithm for inspiration triggering. This interfaces with the vibrating mesh nebulizer module which incorporates a micro-pump chip using piezoelectric effects to eject fluid through a mesh aperture plate holes. By detecting the onset of inspiration based on characteristic acoustic patterns using machine learning models, the controller module sends signals activating the piezoelectric vibration mechanism to generate aerosol only during the inspiratory phase through precision timing control, shutting off mist during expiration. The core module is attached to a standard commercial vibrating mesh nebulizer using the standard adult reusable mouthpiece interface.
Other Names:
  • Microbase, Model Number MBPN002 with trigger system

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary salbutamol concentration
Time Frame: Urine samples will be collected at 30 minutes before nebulization, at 30 minutes, and 24 hours after nebulization.
Quantitative measurement of salbutamol levels in urine samples at protocol-specified timepoints before and after nebulized bronchodilator administration using high performance liquid chromatography (HPLC).
Urine samples will be collected at 30 minutes before nebulization, at 30 minutes, and 24 hours after nebulization.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heart rate
Time Frame: Heart rate will be recorded continuously from 5 minutes before, during, and 30 minutes, and after nebulization.
Heart rate measured via continuous telemetry
Heart rate will be recorded continuously from 5 minutes before, during, and 30 minutes, and after nebulization.
Blood pressure
Time Frame: Blood pressure will be recorded from 5 minutes before, during, and 30 minutes after nebulization.
Systolic and diastolic blood pressure
Blood pressure will be recorded from 5 minutes before, during, and 30 minutes after nebulization.
Saturation
Time Frame: Oxygen saturation will be recorded from 5 minutes before, during, and 30 minutes after nebulization.
Oxygen saturation using a pulse oximeter.
Oxygen saturation will be recorded from 5 minutes before, during, and 30 minutes after nebulization.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Hui-Ling Lin, Chang Gung University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

May 15, 2024

Study Completion (Estimated)

May 24, 2024

Study Registration Dates

First Submitted

November 25, 2023

First Submitted That Met QC Criteria

December 3, 2023

First Posted (Actual)

December 6, 2023

Study Record Updates

Last Update Posted (Actual)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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