NCT06800274

Clinical and Biological Evaluation of NAAGA Versus Azelastine Eye Drops in Allergic Subjects With Tear Film Dysfunction

A Randomized, Single-Blind Clinical Investigation to Compare the Efficacy and Safety of N-Acetyl-Aspartyl-Glutamate (NAAGA) Versus Azelastine Eye Drops in Patients With Allergic Conjunctivitis Associated With Tear Film Dysfunction

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 134 (actual)
• Sponsor: Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized, single-blind study aims to compare the efficacy and safety of N-acetyl-aspartyl-glutamate (NAAGA) and azelastine hydrochloride eye drops in patients with allergic conjunctivitis associated with tear film dysfunction. A total of 134 atopic patients with mild-to-moderate tear film dysfunction were included. Participants were randomly assigned to receive either NAAGA (49 mg/mL, four times daily) or azelastine (0.05%, twice daily) for four weeks. The primary endpoint is the change in Ocular Surface Disease Index (OSDI) scores from baseline to week 4. Secondary endpoints include tear osmolarity, Schirmer test results, tear break-up time (TBUT), MMP-9 levels, and corneal staining scores. This study seeks to provide evidence for the tailored management of allergic conjunctivitis and tear film dysfunction.

Detailed description

There is limited but growing evidence in the literature regarding the effectiveness of N-acetyl-aspartyl-glutamate (NAAGA) in managing allergic conjunctivitis, particularly in patients with concomitant tear film dysfunction. NAAGA is a neuropeptide with dual activity as a mast cell stabilizer and anti-inflammatory agent, reducing histamine release and mitigating inflammatory cascades such as leukotriene production and complement activation. These mechanisms address both the allergic and inflammatory components of ocular surface diseases. Despite its promising therapeutic potential, studies directly comparing NAAGA to other treatments, particularly H1 receptor antagonists like azelastine, remain scarce. In previous studies, NAAGA has demonstrated efficacy in reducing ocular surface inflammation, improving tear film stability, and alleviating symptoms of dry eye disease (DED). It has been reported a significant reduction in inflammatory markers, such as HLA-DR expression, and improvement in tear break-up time (TBUT) and Ocular Surface Disease Index (OSDI) scores in patients treated with NAAGA. Another investigation comparing NAAGA to cyclosporine A noted faster symptom relief and fewer adverse effects with NAAGA, highlighting its tolerability and potential for broader application. However, the literature lacks robust, head-to-head comparisons of NAAGA with second-generation antihistamines, such as azelastine, in the context of allergic conjunctivitis with tear film dysfunction. Based on this background, this randomized, single-blind trial is designed to compare the efficacy and safety of NAAGA (49 mg/mL) with azelastine hydrochloride (0.05%) in treating patients with mild-to-moderate allergic conjunctivitis associated with tear film dysfunction. Both treatments target key mechanisms of disease but differ in their primary mode of action. NAAGA offers dual anti-inflammatory and mast cell-stabilizing effects, while azelastine acts predominantly as an H1 receptor antagonist with additional mast cell stabilization. The primary objective of this study is to demonstrate that NAAGA is non-inferior to azelastine in improving symptoms and clinical parameters of allergic conjunctivitis associated with tear film dysfunction. Specifically, the study will evaluate changes in the Ocular Surface Disease Index (OSDI) score over four weeks of treatment. Secondary objectives include assessing changes in tear osmolarity, TBUT, Schirmer test results, MMP-9 levels, and corneal staining scores, as well as patient-reported symptoms of ocular discomfort. This trial will include 134 patients with atopy and mild-to-moderate tear film dysfunction, randomized to receive either NAAGA eye drops (administered four times daily) or azelastine eye drops (administered twice daily) for four weeks. Both groups will undergo comprehensive evaluations, including the OSDI questionnaire, tear osmolarity testing, Schirmer I test, TBUT measurement, MMP-9 assessment, and fluorescein staining of the ocular surface. Patient-reported discomfort will be tracked through weekly diaries. The investigation is expected to provide critical insights into the comparative efficacy and safety of NAAGA and azelastine in this patient population. NAAGA's dual-action profile may offer broader therapeutic benefits, particularly in addressing inflammation-driven tear film instability and ocular surface damage. Results from this study could inform clinical decision-making and support the development of more targeted, personalized treatments for patients with allergic conjunctivitis and tear film dysfunction.

Conditions

• Allergic Conjunctivitis
• Dry Eye Disease (DED)

Interventions

Type	Name	Description
DRUG	NAAGA (N-acetyl-aspartyl-glutamate) 49 mg/mL	80 patients were randomly assigned to NAAGA in single dose (49 mg/mL), instilled as 1 drop per eye four times daily for four weeks. Specific diagnostic tests and procedures for dry eye disease were performed at week 0 (baseline), week 2 and week 4.
DRUG	azelastine hydrochloride 0.05%	54 patients were randomly assigned to azelastine hydrochloride 0.05% instilled as 1 drop per eye 2 times a day in the conjunctival sac for for four weeks. Specific diagnostic tests and procedures for dry eye disease were performed at week 0 (baseline), week 2 and week 4.

Timeline

• Start date: 2023-04-21
• Primary completion: 2024-03-28
• Completion: 2024-03-28
• First posted: 2025-01-29
• Last updated: 2025-07-15

Locations

1 site across 1 country: Italy