A Randomized, Efficacy Assessor-Blinded, Study to Assess Preliminary Efficacy and Safety of EDTA Eye Drops v. an Active Comparator in the Suppression of Herpes Simplex Virus Eruptions in Subjects With a History of Herpes Labialis

1.1 Background and Rationale Herpes simplex virus (HSV) infections are common and can cause significant morbidity both at the time of the original infection and when recurrences occur. There are two types of HSV - HSV-1 and HSV-2. HSV-1, the most common cause of oral "cold sores," is transmitted mainly by oral-to-oral contact. Genital herpes is usually caused by HSV-2, although HSV-1 can also cause genital breakouts. Both HSV-1 and HSV-2 infections are lifelong, with the virus living in the ganglia of nerves that supply the area of the original infection and recurring sporadically in the same area of that nerve's innervation. Most infections and recurrences are asymptomatic, but infectious viral shedding can occur. Patients who are not asymptomatic can develop prodromes of tingling, pain or paresthesia, and eventually blisters and ulcerations with pain. Healing generally occurs within 10 to 19 days after onset in primary infection or within 5 to 10 days in recurrent infection. Lesions usually heal completely, but recurrent lesions at the same site may cause atrophy and scarring.

According to WHO, in 2012 an estimated 3.7 billion people under age 50 (67%) had HSV-1 infection globally. Some patients have predictable outbreaks after exposure to noxious stimuli, such as sunlight fever, menstruation, or stress.

Researchers have found that calcium signaling is involved in the translocation of the virus from the ganglia to the eruption site. It has been found that an increase of calcium levels in the extracellular matrix will precipitate the calcium signaling events that are causal to the migration of the HSV virus from the proximal ganglia to the eruption site. (Hunsperger 2003, Cheshenko 2003) Further, Husperger found in her experiments (in vitro) that the chelation of calcium greatly reduced the reactivation of the HSV virus.

EDTA Eye Drops (EED), which consists of a calcium chelator and a permeation enhancer, could be one such intervention. Livionex has had some anecdotal evidence that this intervention could work at preventing an HSV eruption and post prodromal viral shedding.

IRB-approved clinical studies of HSV-1 have been performed in normal human volunteers with a history of HSV-1, who develop recurrences with prodromes after exposure to UV light. We will use this technique to induce recurrences in susceptible, HSV-1 infected individuals then treat with EED or Comparator 5 times daily.