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

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

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.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinoconjunctivitis
• Intervention / Treatment: Dietary supplement: Lertal® + standard therapy; Other: Placebo + standard therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80138
    • Az. Osp. Univ. dell'Università degli Studi della Campania "Luigi Vanvitelli"
  • (pv)
    • Pavia, (pv), Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo
  • AQ
    • L'Aquila, AQ, Italy, 67100
      • Ospedale regionale San Salvatore - ASL 1 Avezzano Sulmona L'Aquila
  • BA
    • Bari, BA, Italy, 70126
      • A.O.U. Consorziale "Policlinico Giovanni XXIII"
    • Bari, BA, Italy, 70126
      • A.O.U. Consorziale "Policlinico-Giovanni XXIII"
  • CT
    • Catania, CT, Italy, 95123
      • A.O.U. Policlinico Vittorio Emanuele
  • GE
    • Genova, GE, Italy, 16132
      • Istituto Giannina Gaslini
  • KR
    • Crotone, KR, Italy, 88900
      • P.O. San Giovanni di Dio - ASP di Crotone
  • ME
    • Messina, ME, Italy, 98124
      • A.O.U. Policlinico "G. Martino"
  • MI
    • Garbagnate Milanese, MI, Italy, 20042
      • P.O. G. Salvini di Garbagnate Milanese - ASST Rhodense
    • Legnano, MI, Italy, 20162
      • Ospedale Civile di Legnano - ASST Ovest Milanese
    • Milano, MI, Italy, 20122
      • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
    • Milano, MI, Italy, 20157
      • Ospedale San Carlo Borromeo - ASST Azienda Socio Sanitaria Territoriale Santi Paolo E Carlo
    • Sesto San Giovanni, MI, Italy, 20099
      • Ospedale Città di Sesto San Giovanni - ASST Nord Milano
  • RC
    • Polistena, RC, Italy, 89024
      • Ospedale di Polistena "Santa Maria degli Ungheresi" - ASP di Reggio Calabria
  • RM
    • Roma, RM, Italy, 00161
      • A.O.U. Policlinico Umberto I
  • VA
    • Busto Arsizio, VA, Italy, 21051
      • P.O. di Busto Arsizio - ASST Valle Olona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lertal® + standard therapy; Lertal® double-layer tablets (1 tab/day for 4 weeks) plus standard therapy (antihistamine)	Dietary supplement: Lertal® + standard therapy; 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.
Placebo Comparator: Placebo + standard therapy; Placebo tablets (1 tab/day for 4 weeks) plus standard therapy (antihistamine)	Other: Placebo + standard therapy; Placebo tablet identical in appearance, size and taste to Lertal® tablets. Standard therapy: antihistamine. Standard therapy: antihistamine

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) recorded throughout the study	The incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) recorded throughout the study will be presented overall and by treatment group respectively.	From baseline to Visit 6 (Week 16)
Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) total score	The Pediatric Rhinoconjunctivitis Quality of Life Questionnaire consists of 23 questions in 5 domains (nasal symptoms, ocular symptoms, practical issues, limitation of activities, other symptoms), that are answered on a 7-point scale (0-6), where 0 represents the absence of problems and 6 the greatest symptom distress. Changes from baseline of the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire total score will be calculated at Visit 4 (Week 4) and at Visit 5 (Week 8) or Visit 6 (Week16). An analysis of variance for repeated measures will be adopted, isolating the variability due to type of allergy, treatment group, time of observation and their interaction.	At Baseline, at Visit 4 (Week 4) and at Visit 5 (Week 8) or Visit 6 (Week 16)

Collaborators and Investigators

• Sponsor: NTC srl
• Investigators: Principal Investigator: Gian Luigi Marseglia, Prof., Fondazione IRCCS Policlinico San Matteo di Pavia

Publications and helpful links

General Publications

• Marseglia G, Licari A, Leonardi S, Papale M, Zicari AM, Schiavi L, Ciprandi G; Italian Study Group on Pediatric Allergic Rhinoconjunctivitis. A polycentric, randomized, parallel-group, study on Lertal(R), a multicomponent nutraceutical, as preventive treatment in children with allergic rhinoconjunctivitis: phase II. Ital J Pediatr. 2019 Jul 18;45(1):84. doi: 10.1186/s13052-019-0678-y.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2017
• Primary Completion (Actual): July 4, 2018
• Study Completion (Actual): November 13, 2018

Study Registration Dates

• First Submitted: November 22, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 7, 2017

Study Record Updates

• Last Update Posted (Actual): November 15, 2018
• Last Update Submitted That Met QC Criteria: November 14, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Hypersensitivity; Conjunctival Diseases; Conjunctivitis; Conjunctivitis, Allergic
• Other Study ID Numbers: LER 02-2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No