Clinical trial NCT06157515: Inhaled Dose Analysis Using a Breath Actuated Nebulizer in Healthy Subjects
Official title: Inhaled Dose Analysis Using a Breath Actuated Nebulizer in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Aerosol Therapy
Inhaled Drug Dose
Pharmacogenomic Drug Interaction
Keywords: Vibrating Mesh Nebulizer
Breath-actuated Nebulization
Lead sponsor: Chang Gung University
Sponsor class: OTHER
Collaborators: name: National Tsing Hua University
name: Chang Gung Memorial Hospital
name: National Science and Technology Council
First posted: 2023-12-06
Enrollment: 25
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a prospective crossover interventional study comparing two vibrating mesh nebulizer modalities - continuous versus breath-actuated - for delivering a bronchodilator, tested in healthy adult volunteers. Participants will receive an approved therapeutic dosage (2.5 mg salbutamol) via both devices in an alternating sequence. Outcome measurements focus on pharmacokinetic results, specifically urinary drug recovery.
Primary purpose: DEVICE_FEASIBILITY

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Urinary salbutamol concentration
timeFrame: Urine samples will be collected at 30 minutes before nebulization, at 30 minutes, and 24 hours after nebulization.
Secondary outcomes:
measure: Heart rate
timeFrame: Heart rate will be recorded continuously from 5 minutes before, during, and 30 minutes, and after nebulization.
measure: Blood pressure
timeFrame: Blood pressure will be recorded from 5 minutes before, during, and 30 minutes after nebulization.
measure: Saturation
timeFrame: Oxygen saturation will be recorded from 5 minutes before, during, and 30 minutes after nebulization.
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung University
name: Hui-Ling Lin, PhD
role: STUDY_DIRECTOR
affiliation: Linko Chang Gung Memorial Hospital
name: Li-Chun Chiu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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