A Pilot Study of the Safety, Tolerability, and Effectiveness of Halo to Prevent Acute Upper Respiratory Disease and Respiratory Virus Infections

Significance and Background Respiratory tract disease is a major cause of morbidity and mortality throughout the world accounting for approximately 4 million deaths worldwide. Asthma, pneumonia, and acute bronchiolitis account for almost 22% of all pediatric hospitalizations in the United States. Pneumonia remains in the top ten causes for admission across all age groups in the United States. Much of which are directly caused by, or triggered from respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV), and adenovirus. In addition to these well-known pathogens, advancements in molecular and genomic techniques have increased our detection and identification of new respiratory viruses which also contribute to respiratory disease. There is also renewed attention on respiratory viruses previously considered benign, including the human rhinovirus and coronaviruses, as there is mounting evidence that these viruses can also lead to clinically severe disease. Influenza is one of the leading causes of infectious related deaths and hospitalizations in children and the 2009-10 H1N1 pandemic was especially severe in younger populations.

Respiratory disease can be caused by a variety of micro-organisms especially viruses. Despite the frequency and burden of acute respiratory infections worldwide and across all age groups, there has been limited progress in the management of treatment of respiratory virus infections aside from the use of anti-influenza drugs. The ability to prevent of acute respiratory disease has also been more limited except for the use of the influenza vaccine. The availability of a product that can be used with ease, is low cost but possesses broad spectrum antimicrobial and antiviral activity could play a major role in reducing the overall occurrence, morbidity and mortality associated with acute respiratory disease.

Moreover, upper respiratory infections are the leading cause of outpatient illness in U.S. military professionals and serve as the single greatest cause of lost workdays in the military. Unfortunately, these infections are not only prevalent, but also severe, constituting a primary cause of infectious disease hospitalization in U.S. military personnel including Navy shipboard and submarine personnel, and new recruits at basic training facilities. Military trainees and newly-mobilized troops are particularly subject to upper respiratory infection epidemic outbreaks due to their crowded living conditions, stressed working environments, and exposure to respiratory pathogens in disease-endemic areas. Additionally, the pulmonary disease resulting from ubiquitous infections are particularly impactful in high altitudes and other extreme environments common to Air Force/Navy activities.

Oasis Health Care has developed a technology and product that combines microbial barrier abilities along with a broad spectrum anti-infective agent cetylpyridinium chloride (CPC) at 0.1%. This formulation called Halo is commercially available for the over-the-counter treatment of xerostomia. The spray formulation has high mucoadhesion properties and prolonged retention time in the oral cavity. Cetylpyridinium chloride like chlorhexidine is a quarternary ammonium salt. However, due it possesses certain advantages over the latter in that it targets pathogenic bacteria while sparing beneficial ones (see below). Due to its chemical structure, CPC demonstrates significant antiviral activity especially against respiratory viruses (see below). Toxicology studies have shown no evidence of acute or chronic toxicity in animal models or irritant effect, and over-the-counter mouthwashes containing cetylpyridinium chloride have been marketed for over 45 years. Expanding the indications for the use of a cetylpyridinium-based spray formulation (Halo) as a potential formulation to prevent respiratory virus infections (cold and flu) is the long term goal. This proposal will examine the effect of Halo on the frequency and duration of clinically apparent acute respiratory infections and on respiratory virus burden as measured by PCR in young healthy adults through the respiratory virus season in Cleveland, Ohio.

Selection and enrollment of participants Study Enrollment and Withdrawal One hundred two healthy male and female participants, ages 18-45 will be enrolled in two groups. It is estimated that 204 subjects will need to be screened (2:1 screened to eligible) to enroll 102 subjects. At screening/enrollment, subjects will be stratified as to whether they received inactivated or live influenza virus vaccination. Subjects will be recruited through customary IRB-approved methods. Children, pregnant women, prisoners and other vulnerable individuals will not be enrolled.