The aim of the study is to assess the effect of polyvalent mechanical bacterial lysate (PMBL, Ismigen) on the clinical course of grass pollen-induced allergic rhinitis (using: total nasal symptom score, visual analogue scale, peak nasal inspiratory flow measurement) in children aged 5 to 17 and to assess changes in the concentration of iNKT cells under the influence of the therapy. Half of the 80 participants will receive PMBL while the other half will receive placebo.
Seasonal allergic rhinitis (SAR) is caused by the allergens of wind-pollinated plants, and in Poland mainly by grass pollen allergens. During the grass pollen season, patients may suffer from fatigue, weakness, lack of fitness, difficulty in sleeping and reduced performance at school. In people allergic to the above-mentioned pollen, the disease significantly reduces the quality of life and requires intensive treatment in the pollen period. 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.
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).
Matched tablets without any active substance.
Department of Pulmonary Diseases and Children Rheumatology, Medical University of Lublin
Lublin, Poland
Change in the severity of nasal SAR symptoms as assessed by total nasal symptom score (TNSS)
The severity of nasal SAR symptoms (sneezing, runny nose, itchy nose and nasal congestion) will be recorded by parents of children in the daily patient diary using the following scale: 0 = absent (no symptom); 1 = mild (symptom present, easily tolerated); 2 = moderate (awareness of symptom, bothersome but tolerable); 3 = severe (symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 (no symptoms) to 12 (worst symptoms). Weekly average TNSS values from the baseline period (before the grass pollen season) and obtained 1 month, 2 months, 3 months, 4 months and 5 months after initiating therapy will be used for statistical analysis.
Time frame: at baseline, at 1-month, at 2-months, at 3-months, at 4-months and at 5-months
Change in the nasal obstruction using peak nasal inspiratory flow (PNIF)
Assessment of the nasal obstruction during two site visits based on measurement of peak nasal inspiratory flow by Youlten Peak Flow Meter (Clement Clarke International, UK). The higher PNIF value, the smaller nasal obstruction.
Time frame: at baseline and at 3-months
Change in the severity of nasal SAR symptoms as assessed by visual analogue scale (VAS)
Assessment of the severity of nasal SAR symptoms during six visits (2 site visits and 4 telephone visits) with the use of visual analogue scale.The patient will be asked to indicate the severity of nasal SAR symptoms on a 100 mm visual analogue scale, where 0 is no symptoms and 100 the worst possible symptoms.
Time frame: at baseline, at 1-month, at 2-months, at 3-months, at 4-months and at 5-months
iNKT1 cells concentration
To assess the change in the level of iNKT1 cells (T-bet+IFN-γ+) in the blood.
Time frame: at baseline and at 3-months
iNKT2 cells concentration
To assess the change in the level of iNKT2 cells (GATA3+IL-4+) in the blood.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
Time frame: at baseline and at 3-months
iNKT10 cells concentration
To assess the change in the level of iNKT10 cells (E4BP4+IL-10+) in the blood.
Time frame: at baseline and at 3-months
iNKT17 cells concentration
To assess the change in the level of iNKT17 cells (RORγt+IL-17+) in the blood.
Time frame: at baseline and at 3-months
iNKTreg cells concentration
To assess the change in the level of iNKTreg cells (FoxP3+) in the blood.
Time frame: at baseline and at 3-months
Frequency of oral H1-antihistamines use
To assess the mean number of days of oral H1-antihistamines use for the relief of SAR symptoms.
Time frame: from baseline, up to the 5-month time point
Frequency of intranasal corticosteroids use
To assess the mean number of days of intranasal corticosteroids use for the relief of SAR symptoms.
Time frame: from baseline, up to the 5-month time point
Incidence of treatment emergent adverse events [safety and tolerability]
Incidence, frequency and severity of treatment emergent adverse events.
Time frame: from baseline, up to the 5-month time point
Incidence of treatment emergent adverse events leading to discontinuation [safety and tolerability]
The number of participants with adverse events leading to discontinuation.
Time frame: from baseline, up to the 5-month time point
Time to discontinuation due to treatment emergent adverse events [safety and tolerability]
To assess the time that has elapsed since treatment initiation to the occurrence of an adverse event leading to discontinuation.
Time frame: From date of randomization until the date of occurrence of an adverse event leading to discontinuation, assessed up to 5 months
Incidence of treatment emergent abnormalities in physical examination findings [safety and tolerability]
Observe skin, lymph nodes, ears, eyes, nose, throat, cardiac and pulmonary status, abdomen and extremities for any abnormalities.
Time frame: at baseline and at 3-months
Incidence of treatment emergent abnormalities in pulse rate [safety and tolerability]
Measure resting pulse rate as beats per minute.
Time frame: at baseline and at 3-months
Incidence of treatment emergent abnormalities in blood pressure [safety and tolerability]
Measure systolic and diastolic blood pressure (in mmHg).
Time frame: at baseline and at 3-months