Topical Probiotic Sinus Irrigations for Treating Chronic Sinusitis

Overview

The purpose of this non-randomized study will be to determine whether topical probiotic sinus irrigations are more effective compared to saline sinus irrigation controls in the treatment of active CRS in patients who have had prior sinus surgery based on subjective and objective outcome measures.

Full Title of Study: “Topical Probiotic Sinus Irrigations for the Treatment of Chronic Rhinosinusitis: a Double Blinded Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: December 1, 2023

Detailed Description

CRS is a common clinical entity with estimated prevalence ranging from 14-16% in the community. The most commonly implicated pathogenic bacteria in recalcitrant patients are Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In recent years, there has been an increasing focus on the commensal sinonasal microbiome and its role in the development of a functional immune system. It has been theorized that infections in CRS may be related to a decrease in diversity of the commensal microbiome and an increase in these pathogenic bacteria. The concept behind the therapeutic potential of topical probiotics is that they outcompete pathogenic bacteria via a variety of mechanisms, including creating suboptimal environmental conditions, competing for cell surface receptors and thus limiting pathogen adherence, and producing antibacterial metabolites. In doing so, topical probiotics restore the commensal microbiome. For this study, after being informed about the study and potential risks, all patients meeting eligibility criteria and giving written informed consent will be randomized in a double blind manner (participant and investigator) in a 1:1 ratio to Lactobacillus sakei (1×10(9) CFU L. Sakei nasal irrigation in 240 ml water/irrigation) or Isotonic saline solution in 240 ml of water for nasal irrigation, twice a day for 14 days. Patient assessments will occur before treatments begin, immediately after the completion of nasal irrigations, and 6 weeks after initial enrollment. Assessments will be based on patient history, endoscopic exams, CT scan assessments using Lund-MacKay CT staging system, culture swab of the sinuses (bacterial burden and number of taxa, SNOT-22 survey, and a visual analog scale to record pain scores.

Interventions

  • Drug: Lactobacillus sakei proBio65
    • Lanto Sinus probiotic Lactobacillus sakei is a currently available over the counter supplement from the common source kimchi and produced in South Korea. The product contains 17 billion total CFU of Lactobacillus sakei/gram at the time of manufacture. Lanto Sinus is produced using Good Manufacturing Practice standards. The probiotic is packaged as a powder in PE plastic bottles with 15 grams of product in each bottle. IDS will aliquot 1 gram of product/unlabeled vial, 28 vials/patient. Patients will be instructed to mix 1 vail with 240 mls of distilled water.
  • Other: Isotonic Saline Solution
    • Saline sinus irrigations (SAL group): NeilMed® Isotonic Sinus Rinse™ is marketed as a saline sinus irrigation formula. Subjects will be given instructions to mix one unlabeled vial (containing NeilMed® premixed buffered salt powder) with lukewarm distilled or boiled water in 240mL NeilMed® sinus rinse bottle.

Arms, Groups and Cohorts

  • Active Comparator: Saline Nasal Irrigation (Control)
    • Patients will perform nasal irrigation with an isotonic saline solution, using a 240ml NeilMed sinus rinse bottle, 2 times/day for 14 days. A blinded vial supplied by IDS containing a premeasured amount of saline to be mixed with 240ml of distilled water will be provided to patients for each irrigation.
  • Experimental: Lactobacillus sakei nasal irrigation
    • Patients will perform nasal irrigation with 1 gram of product 2 times/day for 14 days. Each gram of product contains 1×10(9) CFU L. Sakei that will be dissolved in 240 ml water using a 240ml NeilMed sinus rinse bottle. A blinded vial provided by IDS containing a premeasured amount of Lactobacillus sakei to be mixed with 240ml of distilled water will be provided to patients for each irrigation.

Clinical Trial Outcome Measures

Primary Measures

  • Sinonasal Outcome Test-22 (SNOT-22)
    • Time Frame: 6 weeks
    • It is expected that topical probiotic irrigations will result in a clinically significant change in symptom severity score (SNOT-22) (a change of 9 on a scale 0-110) compared to saline irrigations (primary outcome).

Secondary Measures

  • Sinus microbiota
    • Time Frame: 6 weeks
    • Nasal swab samples will be assessed for the number of bacteria present before and after treatment. Bacterial DNA will be extracted from nasal swabs. The purified DNA will be quantified for concentration using a Qubit fluorometer (Invitrogen, CA, USA) before storing at -20°C until further use. Bacterial burden will be determined by quantitative PCR (qPCR) using universal 16S ribosomal RNA primers. Additionally, each nasal swab will be assessed for bacteria taxonomic distribution by NGS using the MiSeq NGS platform (Illumina) before and after treatment. MiSeq paired-end sequencing of the hypervariable V3-V4 regions of the 16S rRNA gene (primers 341F/785R) will be performed.

Participating in This Clinical Trial

Inclusion Criteria

1. Male and female patients 18 years of age or older. 2. Patients diagnosed with acute exacerbation of CRS, defined by worsening of 1 or more sinonasal symptoms (nasal obstruction/congestion, nasal discharge, facial pain/pressure, reduced sense of smell) and inflammatory and/or infectious changes on sinus endoscopy. 3. Patients that have undergone functional endoscopic sinus surgery > 12 weeks prior to enrollment as documented in the patients electronic medical record, with patent sinuses deemed suitable for trial on investigator's discretion. 4. Patients must be willing to follow study related procedures for the duration of the study. 5. Patients must understand the purpose and procedures and be willing to sign the study informed consent document. 6. All adult men and women with active CRS will be considered for participation in this study without regard to race, gender, or socioeconomic status. Exclusion Criteria:

1. Male and female patients under 18 years of age. 2. Patients who have not been diagnosed with CRS or acute exacerbation of CRS, defined by worsening of 1 or more sinonasal symptoms (nasal obstruction/congestion, nasal discharge, facial pain/pressure, reduced sense of smell) and inflammatory and/or infectious changes on sinus endoscopy. 3. Patients that have undergone functional endoscopic sinus surgery < 12 weeks prior to enrollment with patent sinuses deemed unsuitable for trial on investigator's discretion. 4. Patients unwilling to follow study related procedures for the duration of the study. 5. Patients who are unable to independently understand the study purpose and procedures and who are not willing to sign the study informed consent document. 6. Patients who are taking topical antibiotic irrigations and state they are unwilling to stop them. 7. Patients who are unable to complete self-administered questionnaires because of cognitive impairment, language barrier, or severe medical conditions. 8. Patients who have a terminal illness, immunocompromised or systemic disease (e.g. granulomatosis polyangiitis, cystic fibrosis). 9. Patients who have severe or emergent complications from CRS or presence of a sinus tumor. 10. Female patients who are pregnant or breastfeeding. 11. Patients who are taking oral corticosteroids or who have taken oral antibiotics in the previous 2 weeks or on oral corticosteroids.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Illinois at Chicago
  • Collaborator
    • Cures Within Reach
  • Provider of Information About this Clinical Study
    • Principal Investigator: Victoria Lee, Assistant Professor – University of Illinois at Chicago
  • Overall Contact(s)
    • Victoria Lee, MD, 312.996.6582, vlee39@uic.edu

References

Lee VS, Humphreys IM, Purcell PL, Davis GE. Manuka honey sinus irrigation for the treatment of chronic rhinosinusitis: a randomized controlled trial. Int Forum Allergy Rhinol. 2017 Apr;7(4):365-372. doi: 10.1002/alr.21898. Epub 2016 Dec 9.

Ooi ML, Jothin A, Bennett C, Ooi EH, Vreugde S, Psaltis AJ, Wormald PJ. Manuka honey sinus irrigations in recalcitrant chronic rhinosinusitis: phase 1 randomized, single-blinded, placebo-controlled trial. Int Forum Allergy Rhinol. 2019 Dec;9(12):1470-1477. doi: 10.1002/alr.22423. Epub 2019 Aug 28.

Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, Batra PS, Bernal-Sprekelsen M, Bhattacharyya N, Chandra RK, Chiu A, Citardi MJ, Cohen NA, DelGaudio J, Desrosiers M, Dhong HJ, Douglas R, Ferguson B, Fokkens WJ, Georgalas C, Goldberg A, Gosepath J, Hamilos DL, Han JK, Harvey R, Hellings P, Hopkins C, Jankowski R, Javer AR, Kern R, Kountakis S, Kowalski ML, Lane A, Lanza DC, Lebowitz R, Lee HM, Lin SY, Lund V, Luong A, Mann W, Marple BF, McMains KC, Metson R, Naclerio R, Nayak JV, Otori N, Palmer JN, Parikh SR, Passali D, Peters A, Piccirillo J, Poetker DM, Psaltis AJ, Ramadan HH, Ramakrishnan VR, Riechelmann H, Roh HJ, Rudmik L, Sacks R, Schlosser RJ, Senior BA, Sindwani R, Stankiewicz JA, Stewart M, Tan BK, Toskala E, Voegels R, Wang de Y, Weitzel EK, Wise S, Woodworth BA, Wormald PJ, Wright ED, Zhou B, Kennedy DW. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016 Feb;6 Suppl 1:S22-209. doi: 10.1002/alr.21695. Review.

Cervin AU. The Potential for Topical Probiotic Treatment of Chronic Rhinosinusitis, a Personal Perspective. Front Cell Infect Microbiol. 2018 Jan 12;7:530. doi: 10.3389/fcimb.2017.00530. eCollection 2017. Review.

Foreman A, Psaltis AJ, Tan LW, Wormald PJ. Characterization of bacterial and fungal biofilms in chronic rhinosinusitis. Am J Rhinol Allergy. 2009 Nov-Dec;23(6):556-61. doi: 10.2500/ajra.2009.23.3413.

Gasta MG, Gossard CM, Williamson CB, Dolan KE, Finley HJ, Burns CM, Parker EC, Pizano JM, Lipski EA. Probiotics and Disease: A Comprehensive Summary-Part 5, Respiratory Conditions of the Ears, Nose, and Throat. Integr Med (Encinitas). 2017 Jun;16(3):28-40. Review.

Abreu NA, Nagalingam NA, Song Y, Roediger FC, Pletcher SD, Goldberg AN, Lynch SV. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med. 2012 Sep 12;4(151):151ra124. doi: 10.1126/scitranslmed.3003783.

Humphreys GJ, McBain AJ. Antagonistic effects of Streptococcus and Lactobacillus probiotics in pharyngeal biofilms. Lett Appl Microbiol. 2019 Apr;68(4):303-312. doi: 10.1111/lam.13133. Epub 2019 Mar 13.

Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, De Champs C. Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients. Crit Care. 2008;12(3):R69. doi: 10.1186/cc6907. Epub 2008 May 20.

Roos K, Håkansson EG, Holm S. Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. BMJ. 2001 Jan 27;322(7280):210-2.

Roos K, Simark-Mattsson C, Grahn Håkansson E, Larsson L, Sandberg T, Ahrén C. Can probiotic lactobacilli eradicate persistent carriage of meticillin-resistant Staphylococcus aureus? J Hosp Infect. 2011 May;78(1):77-8. doi: 10.1016/j.jhin.2011.01.010. Epub 2011 Mar 2.

Bomer K, Brichta A, Baroody F, Boonlayangoor S, Li X, Naclerio RM. A mouse model of acute bacterial rhinosinusitis. Arch Otolaryngol Head Neck Surg. 1998 Nov;124(11):1227-32.

Prince AA, Steiger JD, Khalid AN, Dogrhamji L, Reger C, Eau Claire S, Chiu AG, Kennedy DW, Palmer JN, Cohen NA. Prevalence of biofilm-forming bacteria in chronic rhinosinusitis. Am J Rhinol. 2008 May-Jun;22(3):239-45. doi: 10.2500/ajr.2008.22.3180.

Rosenfeld RM. Clinical practice guideline on adult sinusitis. Otolaryngol Head Neck Surg. 2007 Sep;137(3):365-77. Review.

Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009 Oct;34(5):447-54. doi: 10.1111/j.1749-4486.2009.01995.x.

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