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

Health, Subjective Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04137029
• Other study ID #: PSRI04-19
• Status: Recruiting
• Phase: N/A
• Start date: April 24, 2019
• Est. completion date: October 2020

Study information

• Verified date: October 2019
• Source: Federal State Budgetary Institution, Pulmonology Scientific Research Institute
• Contact: Kirill A Zykov, Prof
• Phone: +79257729462
• Email: kirillaz[@]inbox.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Bronchial Hyperreactivity
• Health, Subjective
• Hyperreactivity, Bronchial

Intervention

Drug:
• Formoterol
The participants will receive inhalation of formoterol 12 micrograms
• 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

Locations

Country	Name	City	State
Russian Federation	Kirill Zykov	Moscow

Sponsors (4)

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

Country where clinical trial is conducted

Russian Federation, 

References & Publications (3)

Agapova OY, Skoblov YS, Tkachev GA, Mironova NA, Golitsyn SP, Masenko VP, Chazova IE, Zykov KA. [Changes in the receptor activity of ß2-adrenoreceptors of human T-lymphocytes under the effect of ß2-agonists]. Mol Biol (Mosk). 2016 Nov-Dec;50(6):999-1006. — View Citation

Agapova OY, Skoblov YS, Zykov KA, Rvacheva AV, Beilina VB, Masenko VP, Chazova IE. [Radioligand Method of Assessment of ß-Adrenoceptor's Activity on Human T-Lymphocytes]. Bioorg Khim. 2015 Sep-Oct;41(5):592-8. Russian. — View 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 o

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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