Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Activity of Beta-receptors in Healthy Volunteers

Not Applicable

• Conditions: Health, Subjective; Hyperreactivity, Bronchial
• Interventions: Drug: Formoterol; Drug: Tiotropium Bromide; Diagnostic Test: metacholine test

• Registration Number: NCT04137029
• Lead Sponsor: Federal State Budgetary Institution, Pulmonology Scientific Research Institute

Brief Summary

Interventional open-labeled study in parallel groups is aimed to evaluate changes of beta receptors in healthy volunteers under the influence of inhaled metacholine, long-acting anticholinergics and beta-agonists using modified radioligand method.

Detailed Description

Long-acting beta2-agonists and anticholinergics are main drugs in therapy of chronic obstructive pulmonary disease . Beta-agonists exert their bronchodilatory effects via β2 adrenoceptors located on airway smooth muscle cells. Anticholinergics block mainly M3-cholinoreceptors located in the airways, thus inhibiting bronchoconstriction. Metacholine blocks M2-cholinoreceptors thus inducing bronchoconstriction. It is known, that muscarine and beta-receptors interact with each other, but the detailed mechanism is unknown. For evaluating the binding activity of beta-receptors after inhalation of these drugs the modified radioligand method was used.

Study Timeline

• Study Start: 2019-04-24
• Status Verified: 2019-10
• Study First Submitted: 2019-10-11
• Study First Submitted QC: 2019-10-22
• Last Update Submitted: 2019-10-22
• Study First Posted: 2019-10-23
• Last Update Posted: 2019-10-23
• Primary Completion: 2020-07
• Study Completion: 2020-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1 Provision of signed and dated informed consent form 2. Healthy male or female, aged 18-60 years

Exclusion Criteria

• Participants unable to perform spirometry
• Exacerbation respiratory infection within the previous four weeks
• Hypersensitivity or allergy to formoterol, metacholine or tiotropium bromide
• Females who are currently pregnant and lactating
• major surgery in the last 6 months
• Refusal to participate
• Currently participating in another clinical study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
non-smoking	Tiotropium Bromide	Healthy non-smoking volunteers
smoking	Tiotropium Bromide	Healthy smoking volunteers
non-smoking	metacholine test	Healthy non-smoking volunteers
smoking	metacholine test	Healthy smoking volunteers
smoking	Formoterol	Healthy smoking volunteers
non-smoking	Formoterol	Healthy non-smoking volunteers

Primary Outcome Measures

Name	Time	Method
Change from baseline beta-receptor binding activity at 60 min after the inhalation of formoterol or tiotropium.	Baseline (pre-dose), 60 minutes	Beta-receptor binding activity will be measured with modified radioligand method before and after 60 min after the inhalation of formoterol or tiotropium
Change from baseline beta-receptor binding activity at 40 min after the challenge test with metacholine.	Baseline (pre-dose), 40 minutes	Beta-receptor binding activity will be measured with modified radioligand method before and after 40 min after the challenge test with metacholine.

Secondary Outcome Measures

Name	Time	Method
Comparison of beta-receptor binding activity measured with modified radioligand after formoterol and tiotropium.	Baseline (pre-dose), 60 minutes	Difference of change of beta-receptor binding activity measured with modified radioligand method before and after 60 min after the inhalation of formoterol and tiotropium.
Comparison of beta-receptor binding activity measured with modified radioligand method after formoterol or tiotropium in smokers and non-smokers.	Baseline (pre-dose), 60 minutes	Difference of change of beta-receptor binding activity measured with modified radioligand method before and after 60 min after the inhalation of formoterol or tiotropium in smokers and non-smokers.
Comparison of beta-receptor binding activity measured with modified radioligand after metacholine	Baseline (pre-dose), 40 minutes	Difference of change of beta-receptor binding activity measured with modified radioligand method before and after inhalation of metacholine
Comparison of beta-receptor binding activity measured with modified radioligand method after inhalation of metacholine in smokers and non-smokers.	Baseline (pre-dose), 40 minutes	Difference of change of beta-receptor binding activity measured with modified radioligand method before and after inhalation of metacholine

Trial Locations

Locations (1)

Kirill Zykov; 🇷🇺 Moscow, Russian Federation