Decongestant Effect of "Coldamaris Akut", a Carrageenan- and Sorbitol-Containing Nasal Spray in Seasonal Allergic Rhinitis

Abstract

Purpose: This study aimed to develop a hyperosmolar, barrier-forming nasal spray based on carrageenan and sorbitol, and to demonstrate its decongestant effect in the context of allergic rhinitis (AR).

Methods: The efficacy of the nasal spray components was tested in vitro by barrier function, virus replication inhibition, and water absorption assays. The decongestant effectiveness was assessed in a randomized, controlled, crossover environmental chamber trial, where participants with a history of seasonal grass pollen AR were exposed to grass pollen allergens under controlled conditions. Forty-one adults were randomized to receive either carrageenan- and sorbitol-containing nasal spray (CS) or saline solution (SS). After 1 week, participants repeated the exposure with the treatment they had not received before. The primary efficacy endpoint was the mean change in nasal congestion symptom score (NCSS). Secondary efficacy endpoints were nasal airflow, nasal secretion, total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total respiratory symptom score (TRSS).

Results: Preclinical assays demonstrated barrier-building, virus-blocking, and water-withdrawing properties of the CS components. In the clinical study, there was no significant difference in mean NCSS change from pre- to post-treatment between CS and SS. However, nasal airflow increased over time after treatment with CS, while it declined after SS, leading to a growing difference in airflow between CS and SS (p = 0.04 at 6:00 h). Mean nasal secretion over 2-6 h was reduced by ~25% after CS (p = 0.003) compared to pre-treatment, while it was reduced by only ~16% after SS (p = 0.137). No significant differences in TNSS, TOSS and TRSS were observed between CS and SS.

Conclusion: CS improves nasal airflow and reduces nasal secretion in adults with AR. We propose CS as a safe and effective adjuvant to baseline pharmacological treatments.

Trial registration: NCT04532762.

Keywords: Allergic rhinitis; Carragelose; barrier; carrageenan; drug-free; nonpharmacological.

Figure 1

Ex vivo assay – Hyperosmolar effect of CS nasal spray with and without sorbitol. Weight decrease of ex-vivo porcine nasal mucosa after incubation for 1 h at 37°C in CS (carrageenan + 0.5% NaCl + 7% sorbitol in buffered aqueous solution), a 2.4% NaCl solution, or carrageenan + 0.5% NaCl in buffered aqueous solution without sorbitol (CS w/o sorbitol). Error bars represent SD of replicates.

Figure 2

In vitro assay – Barrier function of CS nasal spray. Results of the percentage blocking activity of CS nasal spray relative to negative control (contains sorbitol and NaCl in same concentration as in CS but does not contain the barrier forming component carrageenan). Amounts of barrier-crossing particles were analyzed 3 h after application of beads. Cyan = % blocking activity for particle size of 0.3 µm; blue = % blocking activity for particle size of 1.0 µm. Error bars represent SD of replicates.

Figure 3

Clinical study – Graphical abstract. Panel (A) Study overview. Panel (B) Efficacy assessments carried out per treatment block.

Figure 4

Clinical study – CONSORT flow chart.

Figure 5

Clinical study – NCSS pre- and post-treatment during the grass pollen allergen exposure challenge for the FAS. Panel (A): Baseline corrected mean time course of NCSS. The gray square highlights the timepoints included in the primary efficacy analysis. (B): Primary efficacy analysis: Mean and 95% CI of the difference between treatments in terms of mean NCSS Δ [pre-treatment – ø (2–4 h)]) for the FAS. The mean difference of CS – SS = 0.02, 95% CI [−0.19;0.24], p > 0.05 (paired t-test).

Figure 6

Clinical study – Anterior nasal airflow before and after treatment for the FAS. Mean airflow at timepoints 1 h 30 min (before treatment) and 6 h after start of allergen challenge. Error bars denote 95% CI. P=0.039 for comparison between treatments in difference from pre-treatment to timepoint 6 h.

Figure 7

Clinical study – Mean and 95% CI of the difference between treatments in terms of nasal secretion weight change from pre-treatment to post-treatment for the indicated post-treatment periods for the FAS. Mean difference and 95% CI are given in gram (g). Error bars indicate the 95% CI.