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

NCT ID: NCT06800274

Last Updated: 2025-07-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

134 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-21

Study Completion Date

2024-03-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Allergic Conjunctivitis Dry Eye Disease (DED)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

NAAGA Group

Group Type EXPERIMENTAL

NAAGA (N-acetyl-aspartyl-glutamate) 49 mg/mL

Intervention Type DRUG

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.

Azelastine Group

Group Type ACTIVE_COMPARATOR

azelastine hydrochloride 0.05%

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Adults (≥18 years) with atopy confirmed by skin prick tests, elevated specific IgE levels, or Prist result \>100 kU/L.
* Mild-to-moderate tear film dysfunction defined by OSDI scores ≥13 and at least one diagnostic abnormality (TBUT \<10 sec, Schirmer I test \<10 mm, CLEK score for corneal staining \>1, or tear osmolarity \>308 mOsm/L).

Exclusion Criteria

* Severe ocular surface disorders
* Unilateral dry eye syndrome.
* Recent ocular surgery (within 3 months) or refractive surgery (within 6 months).

. - Active ocular infections.
* Previous herpetic keratitis.
* Systemic or topic therapies with steroids in the last three months.
* Local therapies in the last 14 days.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Mario Troisi

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Mario Troisi, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Universitaria OO.RR. S. Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Azienda Ospedaliera Universitaria OO.RR. S. Giovanni di Dio e Ruggi D'Aragona

Salerno, Salerno, Italy

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Italy

References

Explore related publications, articles, or registry entries linked to this study.

Suarez-Cortes T, Merino-Inda N, Benitez-Del-Castillo JM. Tear and ocular surface disease biomarkers: A diagnostic and clinical perspective for ocular allergies and dry eye disease. Exp Eye Res. 2022 Aug;221:109121. doi: 10.1016/j.exer.2022.109121. Epub 2022 May 21.

Reference Type BACKGROUND
PMID: 35605673 (View on PubMed)

Shin D, Sang Min J. Comparison of treatment effects between 4.9% N-acetyl-aspartyl glutamic acid and 0.05% cyclosporine A eye drops in dry eye patients. Graefes Arch Clin Exp Ophthalmol. 2022 Oct;260(10):3285-3291. doi: 10.1007/s00417-022-05682-x. Epub 2022 Apr 29.

Reference Type BACKGROUND
PMID: 35486175 (View on PubMed)

Regu VR, Swain RP, Subudhi BB. Drug Delivery for Ocular Allergy: Current Formulation Design Strategies and Future Perspectives. Curr Pharm Des. 2023;29(33):2626-2639. doi: 10.2174/0113816128275375231030115828.

Reference Type BACKGROUND
PMID: 37936454 (View on PubMed)

Leonardi A, Quintieri L, Presa IJ, LLoves JM, Montero J, Benitez-Del-Castillo JM, Leston FJS, Gonzalez-Mancebo E, Asero R, Groblewska A, Kuna P. Allergic Conjunctivitis Management: Update on Ophthalmic Solutions. Curr Allergy Asthma Rep. 2024 Jul;24(7):347-360. doi: 10.1007/s11882-024-01150-0. Epub 2024 Jun 13.

Reference Type BACKGROUND
PMID: 38869807 (View on PubMed)

Kumar N, Feuer W, Lanza NL, Galor A. Seasonal Variation in Dry Eye. Ophthalmology. 2015 Aug;122(8):1727-9. doi: 10.1016/j.ophtha.2015.02.013. Epub 2015 Apr 6. No abstract available.

Reference Type BACKGROUND
PMID: 25912217 (View on PubMed)

Janeczko P, Norris MR, Bielory L. Assessment of receptor affinities of ophthalmic and systemic agents in dry eye disease. Curr Opin Allergy Clin Immunol. 2021 Oct 1;21(5):480-485. doi: 10.1097/ACI.0000000000000773.

Reference Type BACKGROUND
PMID: 34387278 (View on PubMed)

James IG, Campbell LM, Harrison JM, Fell PJ, Ellers-Lenz B, Petzold U. Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis. Curr Med Res Opin. 2003;19(4):313-20. doi: 10.1185/030079903125001785.

Reference Type BACKGROUND
PMID: 12841924 (View on PubMed)

Jambou D, Lapalus P. Effect of N-acetyl-aspartyl-glutamate (Naaga) on in-vitro leukotriene synthesis by macrophage cell line P388D1. Int J Tissue React. 1990;12(5):273-80.

Reference Type BACKGROUND
PMID: 1983004 (View on PubMed)

Herrero-Vanrell R, Jauregui Presa I, Leceta Bilbao A, Montero-Iruzubieta J. Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops. J Investig Allergol Clin Immunol. 2023 Dec;33(6):431-438. doi: 10.18176/jiaci.0963.

Reference Type BACKGROUND
PMID: 38095492 (View on PubMed)

Goldschmidt PL, Vulliez-Le Normand B, Briquet I, Dray F. Effects of N-acetyl-aspartyl glutamic acid and sodium cromoglycate on leukotriene B4 secretion by human leukocytes. Allergy. 1990 Jul;45(5):363-9. doi: 10.1111/j.1398-9995.1990.tb00512.x.

Reference Type BACKGROUND
PMID: 2165751 (View on PubMed)

Garcia-Queiruga J, Pena-Verdeal H, Sabucedo-Villamarin B, Garcia-Resua C, Giraldez MJ, Yebra-Pimentel E. Temporal Progression of Entry Factors into the Vicious Circle of Dry Eye in Untreated Sufferers. Life (Basel). 2024 Jun 26;14(7):806. doi: 10.3390/life14070806.

Reference Type BACKGROUND
PMID: 39063561 (View on PubMed)

Fukuda K, Kishimoto T, Sumi T, Yamashiro K, Ebihara N. Biologics for allergy: therapeutic potential for ocular allergic diseases and adverse effects on the eye. Allergol Int. 2023 Apr;72(2):234-244. doi: 10.1016/j.alit.2022.09.005. Epub 2022 Nov 1.

Reference Type BACKGROUND
PMID: 36333219 (View on PubMed)

El Fekih L, Khairallah M, Ben Amor H, Mahmoud A, Chiambaretta F, Messaoud R. Successful management of dry eye disease with a new eye drop formulation combining hyaluronic acid, trehalose, and N-acetyl-aspartyl-glutamic acid (NAAGA). J Fr Ophtalmol. 2024 Sep;47(7):104169. doi: 10.1016/j.jfo.2024.104169. Epub 2024 Jun 4.

Reference Type BACKGROUND
PMID: 38838456 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ASL Napoli 3 sud n. 31/2019

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.