Inhaled Dose Analysis Using a Breath Actuated Nebulizer in Healthy Subjects

Healthy Volunteers Clinical Trial

Official title:

Inhaled Dose Analysis Using a Breath Actuated Nebulizer in Healthy Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06157515
• Other study ID #: BANinHealthy
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: May 24, 2024

Study information

• Verified date: February 2024
• Source: Chang Gung University
• Contact: Hui-Ling Lin, Ph.D
• Phone: +886-3-2118800
• Email: huiling[@]cgu.edu.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 24, 2024
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers
• Respiratory Aspiration

Intervention

Device:
• Breath-actuated vibrating mesh nebulizer
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.
• Continuous vibrating mesh nebulizer
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.

Locations

Country	Name	City	State
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan

Sponsors (3)

Lead Sponsor	Collaborator
Chang Gung University	Chang Gung Memorial Hospital, National Tsing Hua University

Country where clinical trial is conducted

Taiwan, 

References & Publications (21)

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary salbutamol concentration	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	Heart rate	Heart rate measured via continuous telemetry	Heart rate will be recorded continuously from 5 minutes before, during, and 30 minutes, and after nebulization.
Secondary	Blood pressure	Systolic and diastolic blood pressure	Blood pressure will be recorded from 5 minutes before, during, and 30 minutes after nebulization.
Secondary	Saturation	Oxygen saturation using a pulse oximeter.	Oxygen saturation will be recorded from 5 minutes before, during, and 30 minutes after nebulization.