Efficacy and Safety of Lertal® as an add-on to Standard Therapy for Allergic Rhinoconjunctivitis in Pediatrics

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Lertal® as an add-on treatment for children affected by allergic rhinoconjunctivitis.

Detailed Description
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Allergic rhinoconjunctivitis (AR) is a common chronic disorder in children, especially in developed countries. It is not characterized by nasal symptoms only (such as congestion and sneezing), but may also cause general complaints such as fatigue and cough. AR can also have detrimental effects on mood, sleep, social activities and scholastic performance. Lertal® is a novel nutraceutical containing seed extracts from Perilla Frutescens, Quercetin extracted from Sophora japonica and Vitamin D3, all compounds that have demonstrated their ability to reduce allergy symptoms and the use of anti-allergy drugs in adults. The aim of this randomized, double-blinded, parallel-group, placebo-controlled study is to evaluate the efficacy and safety of Lertal® as an add-on treatment for children affected by allergic rhinoconjunctivitis.

Official Title
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A Randomized, Double-blinded, Parallel-group, Placebo-controlled Clinical Study of the Efficacy and Safety of an Oral Nutraceutical (Lertal®) as an add-on to Standard Therapy for Allergic Rhinoconjunctivitis in Pediatrics

Conditions
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Allergic Rhinoconjunctivitis

Intervention / Treatment
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* Dietary Supplement: Lertal® + standard therapy
* Other: Placebo + standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6 to 12 years Male or female Diagnosis of allergic rhinoconjunctivitis Hypersensitivity to dust mites or pollen confirmed with skin-prick test (wheal and redness, ≥ 3 mm more extended than control) performed in the previous 12 months Total Symptoms Score (TSS) ≥ 15 and at least 1 for nasal congestion Written informed consent of patient and of parent or legal guardian Exclusion Criteria: Uncontrolled asthma Secondary rhinitis to other causes Documented evidence of acute or chronic sinusitis Nasal polyps Chronic or intermittent use of inhaled, oral, intramuscular, intravenous or topical corticosteroids Use of leukotriene antagonists Continuous use of antihistamines Inadequate washout of drugs: Systemic or intranasal corticosteroids: 1 month Leukotriene antagonists: 1 month Sodium cromoglycate: 2 weeks Systemic or intranasal decongestants: 3 days Cetirizine, fexofenadine, loratadine, desloratadine, hydroxyzine: 5-10 days Malformations of the nose, ear or throat Upper or lower respiratory tract infection in the last 2 weeks Participation in other clinical studies in the last month Documented hypersensitivity to the study product or its excipients Trip planned outside of the study area

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 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
Interventional Model Description: A randomized, double-blinded, parallel-group, placebo-controlled clinical study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lertal® + standard therapy<br>Lertal® double-layer tablets (1 tab/day for 4 weeks) plus standard therapy (antihistamine) | Dietary Supplement: Lertal® + standard therapy<br>* Lertal® is a novel food supplement. Each tablet contains the following active ingredients: Quercetin 150 mg: a natural flavonoid that inhibits the release of histamine, leukotrienes, PGD2, IL (IL-6, IL-8, TNF-alpha). Perilla frutescens 80 mg: A dry extract of the seeds containing rosmarinic acid, luteolin, apigenin and crysoeriol that inhibits the release of histamine and expression of interleukins (IL-6, TNF-alpha). Vitamin D3 5 mcg (200 IU), which contributes to the normal function of the immune system. Standard therapy: antihistamine.<br>|
| Placebo Comparator: Placebo + standard therapy<br>Placebo tablets (1 tab/day for 4 weeks) plus standard therapy (antihistamine) | Other: Placebo + standard therapy<br>* Placebo tablet identical in appearance, size and taste to Lertal® tablets. Standard therapy: antihistamine. Standard therapy: antihistamine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Symptom Score (TSS) scores | Changes from baseline of Total Symptom Score (TSS) scores will be calculated after 4 weeks of treatment. The Total Symptoms score is a patient-reported evaluation of nine symptoms: Nasal symptoms (Total Nasal Symptom Score): itching, sneezing, rhinorrhea, nasal congestion Ocular symptoms (Total Ocular Symptom Score): itching, hyperemia of conjunctiva, tearing Throat symptoms (Total Throat Symptom Score): itching, coughing With the help of their parents, patients will score symptoms on a 4-point scale: 0 = absent or irrelevant, 1 = mild, 2 = moderate, 3 = severe. Patients are asked to assign a score to the symptoms experienced in the last 12 hours and over the previous two weeks. The total symptom score is the sum of the scores of nasal symptoms, ocular symptoms and throat symptoms. The between-group analysis will be performed by means of a t-test for independent samples or analogous non-parametric test. | At Baseline and after Visit 4 (Week 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale (VAS) score | The patient will be asked to indicate overall system distress on a 100 mm Visual Analogue Scale (VAS) were 0 is equal to no discomfort and 100 the worst possible discomfort. Change from baseline of Visual Analogue Scale (VAS) score after 2 and 4 weeks of treatment. The between-group analysis will be performed using a t-test for independent samples or analogous nonparametric test. | At Baseline, after Visit 3 (Week 2) and after Visit 4 (Week 4) | 
| Total Symptom Score (TSS) scores | Change from baseline of Total Symptom Score (TSS) scores after 2 weeks of treatment. The Total Symptoms score is a patient-reported evaluation of nine symptoms: Nasal symptoms (Total Nasal Symptom Score): itching, sneezing, rhinorrhea, nasal congestion Ocular symptoms (Total Ocular Symptom Score): itching, hyperemia of conjunctiva, tearing Throat symptoms (Total Throat Symptom Score): itching, coughing With the help of their parents, patients will score symptoms on a 4-point scale: 0 = absent or irrelevant, 1 = mild, 2 = moderate, 3 = severe. Patients are asked to assign a score to the symptoms experienced in the last 12 hours and over the previous two weeks. The total symptom score is the sum of the scores of nasal symptoms, ocular symptoms and throat symptoms. The between-group analysis will be performed by means of a t-test for independent samples or analogous non-parametric test. | At Baseline and after Visit 3 (Week 2) | 
| Number of responders (30% reduction of TSS) | Change from baseline of TSS score for each patient after 2 and 4 weeks of treatment will be classified as ≥ 30% and < 30%, thus defining responder and non-responder patients. Between-group differences will be tested by means of a Chi-square test with 2x2 contingency tables. | After Visit 3 (Week 2) and after Visit 4 (Week 4) | 
| Time to maximum effect on Total Symptom Score (TSS) vs placebo | Time to maximum effect on Total Symptom Score (TSS) vs placebo will be analysed by means of t-test for independent samples after logtransformation of the data or analogous non-parametric test. The Total Symptoms score is a patient-reported evaluation of nine symptoms: Nasal symptoms (Total Nasal Symptom Score): itching, sneezing, rhinorrhea, nasal congestion Ocular symptoms (Total Ocular Symptom Score): itching, hyperemia of conjunctiva, tearing Throat symptoms (Total Throat Symptom Score): itching, coughing With the help of their parents, patients will score symptoms on a 4-point scale: 0 = absent or irrelevant, 1 = mild, 2 = moderate, 3 = severe. Patients are asked to assign a score to the symptoms experienced in the last 12 hours and over the previous two weeks. The total symptom score is the sum of the scores of nasal symptoms, ocular symptoms and throat symptoms. | From baseline to Visit 6 (Week 16) | 
| Number of patients using rescue treatment | Between-group differences in the number of patients using rescue treatment will be analyzed by means of a Chi-square test with 2x2 contingency tables. | From baseline to Visit 6 (Week 16) | 
| Total Nasal Symptom Score (TNSS) | The Total Nasal Symptom Score is a patient-reported evaluation of the following symptoms: itching, sneezing, rhinorrhea, nasal congestion. With the help of their parents, patients will score symptoms on a 4-point scale: 0 = absent or irrelevant, 1 = mild, 2 = moderate, 3 = severe. Patients are asked to assign a score to the symptoms experienced in the last 12 hours and over the previous two weeks. Changes from baseline in Total Nasal Symptom Score (TNSS) scores will be calculated after 2 and 4 weeks of treatment and between-group differences analyzed using a t-test for independent samples or analogous non-parametric test. | At Baseline, after Visit 3 (Week 2) and to Visit 4 (Week 4) | 
| Total Ocular Symptom Score (TOSS) | The Total Ocular Symptom Score is a patient-reported evaluation of the following symptoms: itching, hyperemia of conjunctiva, tearing. With the help of their parents, patients will score symptoms on a 4-point scale: 0 = absent or irrelevant, 1 = mild, 2 = moderate, 3 = severe. Patients are asked to assign a score to the symptoms experienced in the last 12 hours and over the previous two weeks. Changes from baseline in Total Ocular Symptom Score (TOSS) scores will be calculated after 2 and 4 weeks of treatment and between-group differences analyzed using a t-test for independent samples or analogous non-parametric test. | At Baseline, after Visit 3 (Week 2) and to Visit 4 (Week 4) | 
| Total Throat Symptom Score (TTSS) | The Total Throat Symptom Score is a patient-reported evaluation of the following symptoms: itching, coughing. With the help of their parents, patients will score symptoms on a 4-point scale: 0 = absent or irrelevant, 1 = mild, 2 = moderate, 3 = severe. Patients are asked to assign a score to the symptoms experienced in the last 12 hours and over the previous two weeks. Changes from baseline in Total Throat Symptom Score (TTSS) scores will be calculated after 2 and 4 weeks of treatment and between-group differences analyzed using a t-test for independent samples or analogous non-parametric test. | At Baseline, after Visit 3 (Week 2) and to Visit 4 (Week 4) | 
| Number of patients symptom-free or with mild symptoms | The number of patients with score for a single symptom ≤ 1 will be calculated and the between-group differences analyzed by means of a Chi-square test with 2xn contingency tables, where n represents the number of observations. | From V3 (Week 2) to Visit 4 (Week 4) | 
| Number of exacerbations | Exacerbations are defined as the need of an antihistamine medication of any kind, at any dose and of any duration. | From Visit 5 (Week 8) to Visit 6 (Week 16) | 
| Intensity (mild, moderate, severe) of exacerbations | Exacerbations are defined as the need of an antihistamine medication of any kind, at any dose and of any duration. | From Visit 5 (Week 8) to Visit 6 (Week 16) | 
| Duration (number of days) of exacerbations | Exacerbations are defined as the need of an antihistamine medication of any kind, at any dose and of any duration. | From Visit 5 (Week 8) to Visit 6 (Week 16) |