Effect of Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Binding Activity of Beta-receptors in Healthy Volunteers
Overview
- Phase
- Not Applicable
- Intervention
- Formoterol
- Conditions
- Health, Subjective
- Sponsor
- Federal State Budgetary Institution, Pulmonology Scientific Research Institute
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Change from baseline beta-receptor binding activity at 60 min after the inhalation of formoterol or tiotropium.
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •1 Provision of signed and dated informed consent form
- •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
Arms & Interventions
smoking
Healthy smoking volunteers
Intervention: Formoterol
smoking
Healthy smoking volunteers
Intervention: Tiotropium Bromide
smoking
Healthy smoking volunteers
Intervention: metacholine test
non-smoking
Healthy non-smoking volunteers
Intervention: Formoterol
non-smoking
Healthy non-smoking volunteers
Intervention: Tiotropium Bromide
non-smoking
Healthy non-smoking volunteers
Intervention: metacholine test
Outcomes
Primary Outcomes
Change from baseline beta-receptor binding activity at 60 min after the inhalation of formoterol or tiotropium.
Time Frame: 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.
Time Frame: 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 Outcomes
- Comparison of beta-receptor binding activity measured with modified radioligand after formoterol and tiotropium.(Baseline (pre-dose), 60 minutes)
- 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)
- Comparison of beta-receptor binding activity measured with modified radioligand after metacholine(Baseline (pre-dose), 40 minutes)
- 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)