Effect of Bacterial Lysate on Nasal Carriage of Staphylococcus Aureus

Study Overview
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Brief Summary
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This study assesses the effectiveness of Polyvalent Mechanical Bacterial Lysate (PMBL-Ismigen) in reducing nasal methicillin-resistant Staphylococcus aureus (MRSA) colony growth in children with pollen allergic rhinitis (AR) aged 5 to 17. Half of the participants received PMBL and the other half received a placebo.

Detailed Description
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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. MRSA colonizing the nasal cavity has the ability to actively modulate the immune response in children suffering from SAR. Many studies have shown a greater severity of AR symptoms in patients with a MRSA-positive nasal swab compared to patients with normal nasal flora. Due to the high incidence of AR, 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, AR, and asthma. Based on the above considerations, it can be hypothesized that bacterial lysates reduce the severity of AR symptoms by eradicating MRSA from the nasal cavity. However, so far no randomized, double-blind, placebo-controlled study has been conducted to evaluate the effect of bacterial lysates on nasal Staphylococcus aureus carriage in children with SAR. The main aim of this study was to evaluate nasal colonization by MRSA among children with SAR and the effect of PMBL on the reduction of MRSA colony growth in these children. 70 children with SAR were enrolled to this study and were randomly assigned to the PMBL group (n=35) and placebo group (n=35). Two visits took place as part of the study: at the beginning of the grass pollen season and at the end of the season. The time frame of the grass pollen season for south-eastern Poland was determined using the 95% method on the basis of measurements of grass pollen concentration in the atmospheric air, which were obtained from the Environmental Allergy Research Centre in Warsaw. Nasal swabs for bacteriological cultures were taken at each visit and were transferred to the hospital laboratory.

Official Title
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The Effect of Polyvalent Mechanical Bacterial Lysate on the Reduction of Nasal Staphylococcus Aureus Carriage in Children With Pollen Allergic Rhinitis

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Drug: Ismigen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children of both genders aged 5 to 17 years. 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. Written informed consent obtained from parents/guardians before any study related procedures are performed. Exclusion Criteria: Patient received mechanical or any other polyvalent bacterial lysate immunostimulation within the previous 12 months before randomisation visit. Patient received oral/subcutaneous allergen-immunotherapy within the previous 3 years before the start of the study. Vaccination performed within 3 months before the beginning of the study. Deficiencies in cellular and humoral immunity. Treatment with antibiotics within the last 1 month before the start of the study. Treatment with systemic corticosteroids within the last 6 months before the start of the study. Pregnant or breastfeeding woman. Other chronic conditions of the nose or nasal sinuses.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ismigen<br>Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest. | Drug: Ismigen<br>* 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) - sublingual use 1 tablet per day over 10 days for 3 successive months.<br>* Other names: Polyvalent Mechanical Bacterial Lysate (PMBL);|
| Placebo Comparator: Placebo<br>Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest. | Drug: Placebo<br>* Matched tablets without any active substance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the growth intensity of the nasal Staphylococcus aureus colony | At the randomization visit and end-of-study visit, a nasal swab was collected for bacteriological cultures and compared whether there was a change in the growth intensity of the Staphylococcus aureus colony between these two points. The collected material was placed in a test-tube with a transport medium and transferred to the laboratory of the University Children's Hospital in Lublin, where it was inoculated on appropriate media. Microbial growth was assessed by semi-quantitative method (+ scanty growth, ++ moderate growth, +++ large growth, ++++ abundant growth). | at baseline, and at 3-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events [safety and tolerability] | Incidence, frequency and severity of treatment emergent adverse events. | from baseline, up to the 3-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. | from baseline, up to the 3-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. | From date of randomization until the date of occurrence of an adverse event leading to discontinuation, assessed up to 3 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. | 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. | 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). | at baseline, and at 3-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allergic rhinitis, seasonal allergic rhinitis, children, grass pollen season, bacterial lysate, nasal Staphylococcus aureus carriage