The Influence of Nonspecific Immunostimulation on Changes in the Concentration of iNKT Cells
Condition: Allergic Rhinitis Due to Grass Pollen
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Ismigen; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Polyvalent mechanical bacterial lysate (PMBL)
Intervention MeSH terms: Broncho-Vaxom
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: allergic rhinitis; seasonal allergic rhinitis; children; grass pollen season; bacterial lysate; iNKT cells