Carrageenan-containing nasal spray alleviates allergic symptoms in subjects with grass pollen allergy: A randomized, controlled, crossover clinical trial

Purpose Nonpharmacological nasal sprays forming a barrier between allergens and the nasal mucosa are used to manage symptoms of allergic rhinitis. We aimed to evaluate the safety and effectiveness of Callergin, a nasal spray containing barrier-forming iota-carrageenan, in the treatment of allergic rhinitis. Methods In this randomized, controlled, crossover trial, we assigned adults with grass pollen allergy to receive Callergin, VisAlpin and no treatment in a random order for three consecutive periods, separated by a washout period of 7 days. Subjects prophylactically applied one puff of nasal spray to each nostril 5-10 minutes prior to challenge. The primary endpoint was mean change from baseline in ‘total nasal symptom score’ (TNSS) over 3 hours, a sum of rhinorrhea, itching, sneezing, and congestion scores, recorded every 15 minutes during the challenge period. Results A total of 42 subjects underwent randomization. Exposure to grass pollen for 3 hours led to a notable TNSS increase from baseline in all subjects at all times. Mean TNSS was lower when subjects received treatment with Callergin compared to no treatment, although the difference did not reach statistical significance (untreated 6.96 ± 2.30; Callergin 6.59 ± 1.93; difference 0.37 points [95% CI -0.17 to 0.91]; p=0.170). In a post-hoc analysis, mean TNSS at 3 hours was significantly reduced with Callergin treatment compared to no treatment (untreated 8.29 ± 2.64; Callergin 7.70 ± 2.56; difference 0.60 points [95% CI -0.10 to 1.29] p=0.028). While all individual nasal symptoms contributed to this effect, rhinorrhea (p=0.013) and congestion (p=0.076) contributed the most. Consistently, nasal secretion weight was slightly reduced with Callergin (p=0.119). VisAlpin improved nasal symptoms, but not significantly in either analysis. The incidence of adverse events was similar among treatment groups. Conclusion Prophylactic treatment with Callergin is safe and alleviates nasal symptoms in adults with grass pollen allergy. Trial registration NCT04531358 ### Competing Interest Statement NU, MM and EP are employees of Marinomed. The other authors have no competing interests in this work. ### Clinical Trial NCT04531358 ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics commitee of Magistrat der Stadt Wien Magistratsabteilung 15-Gesundheitsdienst der Stadt Wien Ethikkommission der Stadt Wien gave ethical approval for this work. EK 19-276-1219 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors