Clinical trial NCT04137029: Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Activity of Beta-receptors in Healthy Volunteers
Official title: Effect of Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Binding Activity of Beta-receptors in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Health, Subjective
Hyperreactivity, Bronchial
Keywords: beta-receptors
metacholine
formoterol
tiotropium
Lead sponsor: Federal State Budgetary Institution, Pulmonology Scientific Research Institute
Sponsor class: OTHER_GOV
Collaborators: name: Moscow State University of Medicine and Dentistry
name: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
name: Branch of Shemyakin-Ovchinnikov Institute of Bioorganic chemistry of RAS
First posted: 2019-10-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There are two groups: the first group is smokers, the second group is non - smokers. The participants of both groups will receive metacholine on the first visit, formoterol 12 micrograms on the second visit, then tiotropium bromide 18 mkg on the third visit.
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline beta-receptor binding activity at 60 min after the inhalation of formoterol or tiotropium.
timeFrame: Baseline (pre-dose), 60 minutes
measure: Change from baseline beta-receptor binding activity at 40 min after the challenge test with metacholine.
timeFrame: Baseline (pre-dose), 40 minutes
Secondary outcomes:
measure: Comparison of beta-receptor binding activity measured with modified radioligand after formoterol and tiotropium.
timeFrame: Baseline (pre-dose), 60 minutes
measure: Comparison of beta-receptor binding activity measured with modified radioligand method after formoterol or tiotropium in smokers and non-smokers.
timeFrame: Baseline (pre-dose), 60 minutes
measure: Comparison of beta-receptor binding activity measured with modified radioligand after metacholine
timeFrame: Baseline (pre-dose), 40 minutes
measure: Comparison of beta-receptor binding activity measured with modified radioligand method after inhalation of metacholine in smokers and non-smokers.
timeFrame: Baseline (pre-dose), 40 minutes
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Kirill Zykov
Study officials:
affiliation: Federal State Budgetary Institution, Pulmonology Scientific Research Institute
name: Kirill A Zykov, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agapova OY, Skoblov YS, Zykov KA, Rvacheva AV, Beilina VB, Masenko VP, Chazova IE. [Radioligand Method of Assessment of beta-Adrenoceptor's Activity on Human T-Lymphocytes]. Bioorg Khim. 2015 Sep-Oct;41(5):592-8. doi: 10.1134/s1068162015050027. Russian.
citation: Agapova OY, Skoblov YS, Tkachev GA, Mironova NA, Golitsyn SP, Masenko VP, Chazova IE, Zykov KA. [Changes in the receptor activity of beta2-adrenoreceptors of human T-lymphocytes under the effect of beta2-agonists]. Mol Biol (Mosk). 2016 Nov-Dec;50(6):999-1006. doi: 10.7868/S0026898416050025. Russian.
citation: Smolyakova E.V., Skoblov Y.S., Skoblova N.A., Agapova O.Y., Ambat'ello L.G., Klimova A.A., Kuznetsova T.V., Masenko V.P., Nistor S.Yu., Rvacheva A.V., Chazova I.E., Zykov K.A. Specificity and Selectivity of the Modified Radioligand Method for Assessment of β1-Adrenoreceptor's Binding Activity on Human T-Lymphocytes. Russian Journal of Bioorganic Chemistry 45(3): 295-301, 2019