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

Allergic Rhinoconjunctivitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03365648
• Other study ID #: LER 02-2017
• Status: Completed
• Phase: N/A
• Start date: September 15, 2017
• Est. completion date: November 13, 2018

Study information

• Verified date: November 2018
• Source: NTC srl
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: November 13, 2018
• Est. primary completion date: July 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Allergic Rhinoconjunctivitis
• Conjunctivitis
• Conjunctivitis, Allergic

Intervention

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.

Other:
• Placebo + standard therapy
Placebo tablet identical in appearance, size and taste to Lertal® tablets. Standard therapy: antihistamine. Standard therapy: antihistamine

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
NTC srl

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)