Association of Cathelicidin and Vitamin D Levels With the Category and Course of COPD (COPD)

Recruitment of patients with COPD. Assessment of clinical status, determination of vitamin D and cathelicidin levels. In the group with vitamin D deficiency, patients receive cholecalciferol (vitamin D) daily for 3 months. After 3 months, the clinical status was assessed again, the level of vitamin D and cathelicidin was determined. When vitamin D levels normalize, cholecalciferol replacement therapy is discontinued for 3 months. After that, a control inspection and laboratory tests are performed.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Chronic Obstructive Pulmonary Disease Moderate; Chronic Obstructive Pulmonary Disease Severe
• Intervention / Treatment: Drug: Cholecalciferol Liquid

Detailed Description

Interventional prospective research design.

The study will be conducted on patients with moderate and severe COPD. The material for the study will be the blood and sputum of patients with COPD.

Research methods: biochemical, enzyme immunoassay, bacteriological, radiological, spirography, clinical, statistical analysis.

The recruitment of patients is carried out in the pulmonology department of the hospital according to the inclusion and exclusion criteria. Patient participation is voluntary. First, the patient is told about the study. If he agrees, he signs an informed consent to conduct research.

Clinical examination of the patient, anthropometry, standard COPD assessment tests will be conducted in the hospital.

Laboratory tests will be conducted in medical institutions in Karaganda and will include a detailed general blood test, determination of fibrinogen and CRP (C-reactive protein) levels, general sputum analysis and bacteriological sputum examination.

Instrumental studies are carried out in medical institutions of the city: spirometry (determination of FEV1 (forced exhalation volume), Gensler index and Tiffno), lung radiography.

The study of vitamin D and cathelicidin is carried out by the ELISA method in the laboratory of the Medical University. Assessment of vitamin D status will be carried out by determining the level of total 25(OH)D (circulating serum, total D2 and D3) with verification of the method relative to international standards (National Institute of Standards and Technology - National Institute of Standards and Technology (NIST), Vitamin D External Quality Assessment Scheme (DEQAS)). The interpretation of vitamin D levels will be carried out according to international standards:

less than 10 ng/ml severe deficiency; 10-20 ng/ml moderate deficiency; 20-30 ng/ml mild deficiency; 30-100 ng/ml Norm; more than 100 ng/ml toxic level.

Quantitative determination of the level of antimicrobial peptide cathelicidin (LL-37) in blood serum will be carried out using enzyme immunoassay (NK321, HumanLL-37 ELISA Kit, Hycult biotech, the Netherlands) in accordance with the manufacturer's instructions. . Normal levels of LL-37: 50-80 ng/ml.

Among the patients with COPD selected at the outpatient stage, persons with vitamin 25(OH) deficiency were identifiedD in the blood (insufficiency/deficiency). In this group, patients received a therapeutic dose of an aqueous solution of cholecalciferol for three months. The therapeutic dose of an aqueous solution of cholecalciferol will be calculated individually according to clinical recommendations for the treatment of vitamin D deficiency and insufficiency.

Patients will continue treatment of the underlying COPD disease according to the clinical protocol. Vitamin therapy is an addition to the main treatment, it should strengthen the immunity and protective abilities of the body. After three months of replacement therapy with cholecalciferol and the next 3 months without it, clinical, laboratory and instrumental research methods will be repeated to assess the effectiveness.

Statistical processing of the research results is supposed to be carried out using statistical packages Excel 2010 (Microsoft, USA), Statistica 10.0 (StatSoft, Inc., USA). Methods of parametric and nonparametric statistics will be used: Student's criterion (t), Mann-Whitney (U), Wilcoxon; correlation analysis with calculation of Spearman's correlation coefficient (R). To compare the case-control groups with a quantitative assessment of the relationship between the factor and the outcome, the odds ratio (OR) with 95% CI will be calculated.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Kazakhstan
  • Karaganda, Kazakhstan, 100000
    • Karaganda Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Clinically confirmed chronic obstructive pulmonary disease

Exclusion Criteria:

• age under 18
• pregnancy
• mental disorders
• cancer
• terminal renal and hepatic insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: normal vitamin D levels; Patients with normal vitamin D levels (30-100ng/ml) No interference is implied. Observation only
Active Comparator: Mild vitamin D deficiency; Patients with mild vitamin D deficiency (20-29 ng/ml)They will receive 4000 IU of cholecalciferol per day for 3 months	Drug: Cholecalciferol Liquid; daily single dose of the drug in the first half of the day in an individually selected dose for 3 months; Other Names: D vitamin
Active Comparator: Moderate vitamin D deficiency; Patients with moderate vitamin D deficiency (10-19 ng/ml) will receive cholecalciferol at a dose of 5000-6000 IU daily for 3 months	Drug: Cholecalciferol Liquid; daily single dose of the drug in the first half of the day in an individually selected dose for 3 months; Other Names: D vitamin
Active Comparator: Severe vitamin D deficiency; Patients with moderate vitamin D deficiency (10-19 ng/ml) will receive cholecalciferol at a dose of 7000-8000 IU daily for 3 months	Drug: Cholecalciferol Liquid; daily single dose of the drug in the first half of the day in an individually selected dose for 3 months; Other Names: D vitamin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamics of vitamin D levels at baseline and 3 months	Assessment of the levels of vitamin D (ng / ml) in blood plasma and evaluate the dynamics of the measurement of the indicator in the same patient in different periods of time, and compare the indicators in groups of patients	At baseline and 3 months
Dynamics of vitamin D levels at baseline and 6 months	Assessment of the levels of vitamin D (ng / ml) in blood plasma and evaluate the dynamics of the measurement of the indicator in the same patient in different periods of time, and compare the indicators in groups of patients	At baseline and 6 months
Dynamics of vitamin D levels at 3 months and 6 months	Assessment of the levels of vitamin D (ng / ml) in blood plasma and evaluate the dynamics of the measurement of the indicator in the same patient in different periods of time, and compare the indicators in groups of patients	At 3 months and 6 months
Dynamics of cathelicidin levels at baseline and 3 months	Assessment of cathelicidin levels (ng / ml) in blood plasma and and evaluate the dynamics of the measurement of the indicator in the same patient in different periods of time, and compare the indicators in groups of patients	At baseline and 3 months
Dynamics of cathelicidin levels at baseline and 6 months	Assessment of cathelicidin levels (ng / ml) in blood plasma and and evaluate the dynamics of the measurement of the indicator in the same patient in different periods of time, and compare the indicators in groups of patients	At baseline and 6 months
Dynamics of cathelicidin levels at 3 months and 6 months	Assessment of cathelicidin levels (ng / ml) in blood plasma and evaluate the dynamics of the measurement of the indicator in the same patient in different periods of time, and compare the indicators in groups of patients	At 3 months and 6 months

Collaborators and Investigators

• Sponsor: Karaganda Medical University

Publications and helpful links

Helpful Links

• Uysal P, Simsek G, Durmus S, Sozer V. Evaluation of plasma antimicrobial peptide LL-37 and nuclear factor-kappaB levels in stable chronic obstructive pulmonary disease 25 January 2019 Volume 2019:14 Pages 321-330
• World Health Organization official website
• International conference "Respiratory Junction Almaty: Where East meets West". 02.04.2019
• Yang YM, Guo YF, Zhang HS, Sun TY. Antimicrobial peptide LL-37 circulating levels in chronic obstructive pulmonary disease patients with high risk of frequent exacerbations. J Thorac Dis. 2015;7(4):740-745
• V. Casanova, F.H. Sousa, C. Stevens, P. Barlow Antiviral therapeutic approaches for human rhinovirus infections Future Virol., 13 (2018), pp. 505-518 CrossRefView Record in ScopusGoogle Scholar
• Roby KD, Nardo AD. Innate immunity and the role of the antimicrobial peptide cathelicidin in inflammatory skin disease. Drug Discov Today Dis Mech. 2013;10(3-4):e79-e82. doi:10.1016/j.ddmec.2013.01.001
• Burkes RM, Astemborski J, Lambert AA, et al. Plasma cathelicidin and longitudinal lung function in current and former smokers. PLoS One. 2019;14(2):e0212628. Published 2019 Feb 27. doi:10.1371/journal.pone.0212628
• Gromova O.A., Vitamin D - paradigm shift [Electronic resource] / Gromova O.A., Torshin I.Yu. - M. : GEOTAR-Media, 2017. - 576 p. - ISBN 978-5-9704-4058-2
• Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention C.F. GARLAND, C.B. FRENCH, L.L. BAGGERLY and R.P. HEANEY Anticancer Research February 2011 vol.31 no.2 6007-611

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2020
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: June 21, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: COPD; vitamin D; cathelicidin; antimicrobial peptide
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: VitD COPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No