The Influence of Nonspecific Immunostimulation on Changes in the Concentration of iNKT Cells
NCT ID: NCT04802616
Last Updated: 2022-04-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
80 participants
INTERVENTIONAL
2021-03-22
2021-10-29
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Efficacy Of Bacterial Lysate In Children With Allergic Rhinitis
NCT04270552
Intralymphatic Immunotherapy With Polvac Grass & Rye Allergen Extract
NCT05297760
Effect of Bacterial Lysate on Nasal Carriage of Staphylococcus Aureus
NCT04637425
Comparison of Perennial and Preseasonal Subcutaneous Immunotherapy
NCT01555736
Safety, Immunological Effect and Efficacy of the Combined Application of MPL and Grass Pollen Allergen
NCT00241410
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Due to the high incidence of allergic rhinitis, the negative impact of the disease on the quality of life, and incomplete effectiveness of previously available therapeutic methods, new methods of treatment are being developed. Recent research highlights the immunoregulatory potential of bacterial lysates, indicating the possibility of their future use in the prevention and treatment of allergic diseases, including atopic dermatitis, allergic rhinitis, and asthma. However, the mechanism of action of these drugs in allergic diseases is still not entirely clear.
iNKT (Invariant Natural Killer T) are a conserved line of T cells with unique features expressing the invariant TCR alpha chain and recognizing glycolipids presented in the context of the non-classical MHC molecule, CD1d. As a result of TCR stimulation, iNKT cells are able to quickly secrete a variety of cytokines, thus stimulating various immune processes and playing an immunoregulatory role. iNKT cells are a small percentage of all T cells, however numerous studies indicate their possible participation in the pathogenesis of allergic diseases.The ambivalence of the activity of iNKT cells may result from the heterogeneity of this subpopulation. iNKT cells, like T lymphocytes, can be divided into further subpopulations: iNKT1, iNKT2, iNKT10, iNKT17 and iNKTreg. Individual subpopulations have a different cytokine profile, and thus may play opposite functions in the pathomechanism of many diseases, including allergic ones.
The main aim of this study is to evaluate the clinical course of the pollen allergic rhinitis, caused by grass pollen allergens in children during the grass pollen season, treated with polyvalent mechanical bacterial lysate (PMBL) and to assess the impact of PMBL on changes in the concentrations of the iNKT cell subpopulation. The approval of the Bioethics Committee at the Medical University in Lublin was obtained for the study.
Eighty children with SAR will be enrolled to this study and randomly assigned to the PMBL group (n=40) and placebo group (n=40). The study will include six visits, 2 site visits (before the grass pollen season and at the peak of the grass pollen season) and 4 telephone visits.The first site visit will be the randomization visit. The second site visit will take place after the end of the drug intake period. Telephone contact with the patient will take place twice during the period of taking the drug, and twice after the end of this period (follow-up visits).The time frame of the grass pollen season for south-eastern Poland will be determined using the "95%" method on the basis of measurements of grass pollen concentration in the atmospheric air, which will be obtained from the Environmental Allergy Research Centre in Warsaw. Patients will start taking sublingual tablets at the beginning of the April 2021.
Nasal SAR symptoms will be recorded by parents of children in the daily patient diary according to the standard scoring system (TNSS, total nasal symptom score), and their intensity will be also evaluated during six visits using VAS (visual analogue scale). At each site visit, peak nasal inspiratory flow (PNIF) will be also measured.
In order to determine the mechanism responsible for the possible effects of PMBL, blood samples (8 ml) will be taken from patients for additional tests during two site visits. The following iNKT cell subpopulations will be measured in the blood: iNKT1, iNKT2, iNKT10, iNKT17 and iNKTreg.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Polyvalent mechanical bacterial lysate
Treatment over 3 successive months with one daily sublingual tablet (7 mg of bacterial lysate) over 10 days followed by 20 days of rest.
Ismigen
Sublingual tablets containing 7 mg of bacterial lysate from the following bacteria: Staphylococcus aureus, Haemophilus influenzae serotype B, Klebsiella pneumoniae, Klebsiella ozaenae, Neiserria catarrhalis, Streptococcus viridans, Streptococcus pyogenes, Streptococcus pneumoniae (6 strains: TY1/EQ11, TY2/EQ22, TY3/EQ14, TY5/EQ15, TY8/EQ23, TY47/EQ24).
Placebo
Treatment over 3 successive months with one daily sublingual tablet over 10 days followed by 20 days of rest.
Placebo
Matched tablets without any active substance.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ismigen
Sublingual tablets containing 7 mg of bacterial lysate from the following bacteria: Staphylococcus aureus, Haemophilus influenzae serotype B, Klebsiella pneumoniae, Klebsiella ozaenae, Neiserria catarrhalis, Streptococcus viridans, Streptococcus pyogenes, Streptococcus pneumoniae (6 strains: TY1/EQ11, TY2/EQ22, TY3/EQ14, TY5/EQ15, TY8/EQ23, TY47/EQ24).
Placebo
Matched tablets without any active substance.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Children with grass pollen-induced allergic rhinitis recognized and treated according to current ARIA (Allergic Rhinitis and its Impact on Asthma) recommendations.
* Positive skin prick test to grass pollen allergens or positive specific IgE (defined as ≥ class 2, ≥ 0,70 kU/l) against timothy grass pollen allergens.
* Presentation of clinical symptoms of the allergic rhinitis (rhinorrhea, nasal congestion, nasal itching, sneezing) in at least two recent grass pollen seasons in Poland before inclusion in the study.
* Proper use of polyvalent mechanical bacterial lysate sublingual tablets.
* Not using drugs to alleviate the symptoms of allergic rhinitis in the last 7 days prior to enrollment in the study: intranasal glucocorticosteroids, intranasal, oral and ophthalmic antihistamines, intranasal and oral alpha-mimetics, intranasal anticholinergics, antileukotrienes and cromones.
* Written informed consent obtained from parents/guardians before any study related procedures are performed.
Exclusion Criteria
* Patient received chemical bacterial lysate immunostimulation within the previous 6 months before randomisation visit.
* Patient received oral/subcutaneous allergen-immunotherapy within the previous 3 years before the start of the study.
* Other chronic conditions of the nose or nasal sinuses.
* Severe nasal septum deviation.
* Acute respiratory infection in the 2 weeks prior to randomization visit.
* Treatment with systemic corticosteroids within the last 6 months before the start of the study.
* History of transfusion of blood, blood components or blood products.
* Pregnant or breastfeeding woman.
* Other chronic, uncontrolled diseases of the respiratory tract, gastrointestinal tract, urinary system, hematological diseases, immunodeficiency, cancer, cystic fibrosis.
5 Years
17 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Medical University of Lublin
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Kamil Janeczek
Principal Investigator
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Department of Pulmonary Diseases and Children Rheumatology, Medical University of Lublin
Lublin, , Poland
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Janeczek K, Emeryk A, Rachel M, Duma D, Zimmer L, Poleszak E. Polyvalent Mechanical Bacterial Lysate Administration Improves the Clinical Course of Grass Pollen-Induced Allergic Rhinitis in Children: A Randomized Controlled Trial. J Allergy Clin Immunol Pract. 2021 Jan;9(1):453-462. doi: 10.1016/j.jaip.2020.08.025. Epub 2020 Aug 26.
Janeczek KP, Emeryk A, Rapiejko P. Effect of polyvalent bacterial lysate on the clinical course of pollen allergic rhinitis in children. Postepy Dermatol Alergol. 2019 Aug;36(4):504-505. doi: 10.5114/ada.2019.87457. Epub 2019 Aug 30. No abstract available.
Banche G, Allizond V, Mandras N, Garzaro M, Cavallo GP, Baldi C, Scutera S, Musso T, Roana J, Tullio V, Carlone NA, Cuffini AM. Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects. Int J Immunopathol Pharmacol. 2007 Jan-Mar;20(1):129-38. doi: 10.1177/039463200702000115.
Meng Q, Li P, Li Y, Chen J, Wang L, He L, Xie J, Gao X. Broncho-vaxom alleviates persistent allergic rhinitis in patients by improving Th1/Th2 cytokine balance of nasal mucosa. Rhinology. 2019 Dec 1;57(6):451-459. doi: 10.4193/Rhin19.161.
Han L, Zheng CP, Sun YQ, Xu G, Wen W, Fu QL. A bacterial extract of OM-85 Broncho-Vaxom prevents allergic rhinitis in mice. Am J Rhinol Allergy. 2014 Mar-Apr;28(2):110-6. doi: 10.2500/ajra.2013.27.4021.
Liu C, Huang R, Yao R, Yang A. The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma. Lung. 2017 Oct;195(5):563-569. doi: 10.1007/s00408-017-0003-8. Epub 2017 May 4.
Esposito S, Soto-Martinez ME, Feleszko W, Jones MH, Shen KL, Schaad UB. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol. 2018 Jun;18(3):198-209. doi: 10.1097/ACI.0000000000000433.
Emeryk A, Bartkowiak-Emeryk M, Raus Z, Braido F, Ferlazzo G, Melioli G. Mechanical bacterial lysate administration prevents exacerbation in allergic asthmatic children-The EOLIA study. Pediatr Allergy Immunol. 2018 Jun;29(4):394-401. doi: 10.1111/pai.12894.
Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol. 2005;23:877-900. doi: 10.1146/annurev.immunol.23.021704.115742.
Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol. 1999 Nov 1;163(9):4647-50.
Oki S, Miyake S. Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases. Allergol Int. 2007 Mar;56(1):7-14. doi: 10.2332/allergolint.R-06-137. Epub 2007 Jan 29.
Bennstein SB. Unraveling Natural Killer T-Cells Development. Front Immunol. 2018 Jan 9;8:1950. doi: 10.3389/fimmu.2017.01950. eCollection 2017.
Gupta RK, Gupta K, Dwivedi PD. Pathophysiology of IL-33 and IL-17 in allergic disorders. Cytokine Growth Factor Rev. 2017 Dec;38:22-36. doi: 10.1016/j.cytogfr.2017.09.005. Epub 2017 Nov 11.
Coomes SM, Kannan Y, Pelly VS, Entwistle LJ, Guidi R, Perez-Lloret J, Nikolov N, Muller W, Wilson MS. CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation. Mucosal Immunol. 2017 Jan;10(1):150-161. doi: 10.1038/mi.2016.47. Epub 2016 May 11.
Janeczek K, Kowalska W, Zarobkiewicz M, Suszczyk D, Mikolajczyk M, Markut-Miotla E, Morawska-Michalska I, Bakiera A, Tomczak A, Kaczynska A, Emeryk A, Rolinski J, Piotrowska-Weryszko K. Effect of immunostimulation with bacterial lysate on the clinical course of allergic rhinitis and the level of gammadeltaT, iNKT and cytotoxic T cells in children sensitized to grass pollen allergens: A randomized controlled trial. Front Immunol. 2023 Jan 17;14:1073788. doi: 10.3389/fimmu.2023.1073788. eCollection 2023.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
KE-0254/251/2020
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.