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

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

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.

Study Overview

• Status: Unknown
• Conditions: Health, Subjective; Hyperreactivity, Bronchial
• Intervention / Treatment: Drug: Formoterol; Drug: Tiotropium Bromide; Diagnostic test: metacholine test

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kirill A Zykov, Prof; Phone Number: +79257729462; Email: kirillaz@inbox.ru
• Study Contact Backup: Name: Anna V Eremenko; Phone Number: +79265598031; Email: a_nn87@list.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115682
    • Recruiting
    • Kirill Zykov
    • Contact: Kirill Zykov, Prof; Phone Number: +74953956393; Email: pulmo_fmba@mail.ru
    • Contact: Anna Eremenko; Phone Number: +79265598031; Email: a_nn87@list.ru
    • Sub-Investigator: Ann Eremenko

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: smoking; Healthy smoking volunteers	Drug: Formoterol; The participants will receive inhalation of formoterol 12 micrograms; Drug: Tiotropium Bromide; The participants will receive inhalation of tiotropium bromide 18 mkg once; Diagnostic test: metacholine test; The participants will receive inhalation of metacholine once
EXPERIMENTAL: non-smoking; Healthy non-smoking volunteers	Drug: Formoterol; The participants will receive inhalation of formoterol 12 micrograms; Drug: Tiotropium Bromide; The participants will receive inhalation of tiotropium bromide 18 mkg once; Diagnostic test: metacholine test; The participants will receive inhalation of metacholine once

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of beta-receptor binding activity measured with modified radioligand after formoterol and tiotropium.	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.	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.	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.	Baseline (pre-dose), 60 minutes
Comparison of beta-receptor binding activity measured with modified radioligand after metacholine	Difference of change of beta-receptor binding activity measured with modified radioligand method before and after inhalation of 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.	Difference of change of beta-receptor binding activity measured with modified radioligand method before and after inhalation of metacholine	Baseline (pre-dose), 40 minutes

Collaborators and Investigators

• Sponsor: Federal State Budgetary Institution, Pulmonology Scientific Research Institute
• Collaborators: Moscow State University of Medicine and Dentistry; National Medical Research Center for Cardiology, Ministry of Health of Russian Federation; Branch of Shemyakin-Ovchinnikov Institute of Bioorganic chemistry of RAS

Publications and helpful links

General Publications

• 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.
• 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.
• 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

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 24, 2019
• Primary Completion (ANTICIPATED): July 1, 2020
• Study Completion (ANTICIPATED): October 1, 2020

Study Registration Dates

• First Submitted: October 11, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (ACTUAL): October 23, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 22, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: formoterol; tiotropium; beta-receptors; metacholine
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchial Hyperreactivity; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tiotropium Bromide; Bromides; Formoterol Fumarate
• Other Study ID Numbers: PSRI04-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No