Xlear have developed and patented a xylitol containing nasal spray for the treatment of
      upper-respiratory tract infections. The nasal spray is comprised of xylitol and GSE
      (Grapefruit Seed extract) which provides antibacterial properties as well as preventing viral
      adhesion in the nasal passage. Studies into Xlear's antiviral effects on SARS-CoV-2 are
      currently ongoing but hypothetically, a Xylitol Based Nasal spray may prove to be a useful
      and inexpensive treatment for COVID-19 infection.

Xylitol Based Nasal Spray for COVID-19 Treatment

Respiratory Viral Infection

1. BACKGROUND and RATIONALE

      In the wake of the Coronavirus disease 2019 (COVID-19) pandemic, worldwide healthcare has
      rapidly evolved in response. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is
      a novel virus responsible for COVID-19, which at the most severe end of the spectrum of
      disease can require hospitalisation or ICU admission. Preventative measures are currently
      being taken with numerous vaccination programs across the world. However, there is currently
      no established treatment for mild COVID-19 infection, i.e., symptomatic infection not
      requiring hospitalisation, which makes up a significant proportion of cases. Xylitol has
      shown promising results in combating SARS-CoV-2 in vitro and this study aims to explore
      whether Xlear's Xylitol based Nasal Spray has an effect in vivo.

      1.1 COVID-19 Infection SARS-CoV-2 is a positive-sense, single-strand RNA virus comprised of
      four structural proteins: Nucleocapsid (N) protein, Membrane (M) protein, Spike (S) protein
      and Envelope (E) protein. These structural proteins play an important role in receptor
      binding, transcription, replication and assembly of the virus in host cells (Boopathi et al.,
      2020). The nasal epithelium acts as the primary site for SARS-CoV-2 binding to angiotensin
      converting enzyme-2 (ACE2) - the receptor responsible for COVID-19 infection (Zhou et al.,
      2020). With nasal carriage playing a vital role in transmission, drugs administered
      intranasally could be a viable therapeutic option (Sungnak et al., 2020).

      1.2 Drug: Xylitol Xylitol is a sugar alcohol derived from plants. It is used in the dental
      profession to prevent plaque build-up and inhibit enamel demineralisation by interfering with
      the metabolism of Streptococcus mutans, causing cell death and thus preventing dental caries
      (Janakiram et al., 2017). Xylitol not only demonstrates antimicrobial behaviour but can also
      modulate immunity and contribute to wound healing (Salli et al., 2019).

      1.2.1 Xylitol and Respiratory Tract Infections Xylitol's inhibitory effect on Streptococcus
      mutans growth has prompted more research into its interactions with other nasopharyngeal
      pathogens responsible for respiratory tract infections. An in vitro study into
      alpha-haemolytic Streptococcus pneumoniae and beta-haemolytic Streptococci treated with 1%
      and 5% xylitol showed statistically significant inhibition of growth over a 24-hour
      incubation period (Kontiokari et al., 1999).

      Another team established xylitol's ability to kill coagulase-negative Staphylococcus. 5%
      xylitol administered to 21 participants compared to a control group using a saline solution
      showed a significant decrease in Staphylococcus count from 597 colony forming units (CFU) per
      swab to 99 CFU per swab (Zabner et al., 2000).

      1.2.2 Xylitol and Viruses Xylitol's inhibitory effects on bacteria are well documented but
      little is known regarding its antiviral properties. Dietary xylitol was used to treat
      influenza A virus in vivo. Mice given a combination of xylitol and red ginseng had 100%
      survival rate at 33mg/kg/day of xylitol and 60% survival rate at 3.3mg/kg/day after day 14 of
      infection versus 0% survival rate on PBS (control), red ginseng and xylitol separately. This
      suggests a synergistic effect between xylitol and red ginseng (Yin et al., 2014).

      A study into xylitol and its interactions with human respiratory syncytial virus (hRSV) was
      conducted in 2015. Xylitol was tested in vitro on a hRSV suspension and in vivo in mice. The
      in vitro effect of xylitol showed complete inhibition at concentrations of 3.13mg/ml. Xylitol
      significantly reduced lung viral titres in mice with 3.3mg/kg/d proving the most effective
      dose (Xu et al., 2016).

      1.3 Grapefruit Seed Extract (GSE) Grapefruit seed extract (GSE) is made from grapefruit
      seeds. It is used as a natural remedy due to its antioxidant and antimicrobial properties
      (Reagor et al., 2002; Salehi et al., 2019).

      1.3.1 GSE and Viruses GSE was tested on multiple viruses to determine if it had any
      inhibitory effects. GSE exhibited virucidal activity against avian influenza virus (AIV) and
      Newcastle disease virus (NDV) but not against infectious bursal disease virus (IBDV) (Komura
      et al., 2019). These findings may be important as AIV and NDV are enveloped viruses like
      SARS-CoV-2 whilst IBDV is not (Schoeman et al., 2019). It could be hypothesised that GSE
      could exhibit similar inhibition on SARS-CoV-2.

      1.4 Xlear's Xylitol based Nasal Spray Xlear have developed and patented a xylitol containing
      nasal spray for the treatment of upper-respiratory tract infections. The nasal spray is
      comprised of xylitol and GSE which provides antibacterial properties as well as preventing
      viral adhesion in the nasal passage. Studies into Xlear's antiviral effects on SARS-CoV-2 are
      currently ongoing but hypothetically, a Xylitol Based Nasal spray may prove to be a useful
      and inexpensive treatment for COVID-19 infection.

      1.4.1 Xlear and Coronavirus Xylitol has been shown to exhibit antiviral properties against
      SARS-CoV-2 in vitro (Bansal et al., 2021; Ferrer et al., 2020).

      USA-WAI/2020 strain was prepared and passaged in Vero 76 cells for testing with Xlear
      (experiment 2) and its components xylitol and GSE separately (experiment 1). GSE 0.2% reduced
      SARS-CoV-2 from 3.67 log10 CCID50/0.1 mL to undetectable in experiment 1. Xlear in virucidal
      assays completely inhibited viral infectively at varying concentrations (90%, 80%, 50%) and
      reduced viral titre by 2.17 log in 20% concentration indicating a dose-dependent response
      (Appendix 1) (Ferrer et al., 2020). A subsequent study showed statistically significant
      reduction in viral titres treated with Xlear nasal spray treatment - 4.2 log10 CCID50/0.1mL
      to 1.7, a reduction of 2.5 log10 CCID50 (Cannon et al., 2020).

      A recent private report by Dr Cagno's team in Lausanne (April 2021) has confirmed the viral
      killing properties of Xlear in 2021 SARS-CoV-2 strains. Viral stocks were grown in Vero E6
      cells belonging to two lineages, B1.1.7 and B1.351. Complete inhibition of viral infectivity
      was observed in 90%, 60% and 20% concentration Xlear virucidal assays for B1.351. Viral
      infectivity was similarly completely inhibited in B1.17 at 90% and 60% concentration with a
      3.06 log reduction at 20% illustrated in Appendix 2.

      A case study was conducted on individuals who had taken Xlear as treatment for COVID-19
      infection. Participants were required to spray into each nostril four times per day (140 µL
      per spray). All individuals showed improvement in symptoms with quicker turnarounds from
      turning positive to negative via COVID-19 reverse transcriptase polymerase chain reaction
      (RT-PCR) nasal swabs. Importantly, some individuals had relevant co-morbidities such as
      current smoking status and obesity. Although it is difficult to attribute symptom improvement
      and viral load decrease to Xlear's spray, it does provide rationale for a double-blind
      placebo controlled randomised clinical trial (Go et al., 2020).

Nasal Spray

Clinical Efficacy of Xylitol Based Nasal Spray for the Treatment of Mild COVID-19 Infection

The between-groups difference in log-viral load over the total treatment period

Proportion of subjects reaching undetectable viral load

The proportion difference in groups requiring hospitalization

Adverse events and discontinuation of nasal spray use

The participants will receive Xylitol based nasal spray

The participants will receive saline based placebo

Xylitol Based Nasal Spray for COVID-19 Treatment

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?