Clinical study summary

STUDY OF THE EFFECT OF intercept^CS™ TOPICAL HEAT IN RECURRENT PERI-BUCCAL HERPES

A multi-centre, double-blind, placebo-controlled study

Professor Loïc Vaillant, Doctor Jean- Paul Deheuvals, Department of Dermatology, Tours Faculty of Medicine, University François Rabelais

Purpose:

To assess the efficacy and tolerability of intercept^CS for the prevention of cold sores in patients suffering from recurrent eruptions.

Method:

A multi-centre, randomized, cross-over, double-blind, placebo-controlled study included 47 herpes simplex patients who had reported at least four outbreaks in the preceding 12 months.

The placebo device was visually identical to intercept^CS and produced heat like intercept^CS but at a low, non-therapeutic temperature.

In Phase I each patient received either placebo or intercept^CS according to a pre-established random order (plus a self report notebook and disposable camera). Patients were instructed to use their test device as follows: three 30-second applications at 5-minute intervals in the first three hours of the prodromal phase.

After a 4 to 6 month test period (and 15 day washout period) patients received the other device for Phase II (also a 4-6 month test period).

Results:

Efficacy: intercept^CS was significantly more effective than placebo in preventing the recurrence of cold sores (46.3% vs. 25.0%) p=0.03.

Tolerability: Tolerance to treatment with intercept^CS (as reported by both patients and physicians) was identical to placebo. The tolerability difference between intercept^CS and placebo was not significant p=0.75

Conclusion:

intercept^CS is the first treatment to demonstrate clinical effectiveness for the prevention of cold sores.

Putative Mechanism of Action

intercept^CS™ is a Class II medical device that uses targeted heat therapy to prevent cold sores.  The intercept^CS Thermal Defence Technology works by enhancing the cell's immune response to viral attack. In a cold sore outbreak, latent herpes simplex virus (HSV) is reactivated from where it is dormant in nerve ganglia near the upper portion of the spinal cord. The virus moves down peripheral nerves to the skin and replicates in the sensory nerve endings, causing the prodromal symptoms of tingling, itching, or burning.

intercept^CS is used at this stage to deliver heat therapy to the affected area. This results in a 'heat shock' response within the skin cells. This response is a well studied phenomenon that protects cells from stress. The production of heat shock proteins is increased in response to heat shock, and some of these proteins participate with the immune system to help recognize and eliminate virally-infected cells.

In order to prevent the development of a cold sore lesion, skin cells infected by HSV must be destroyed early after the virus is reactivated from latency, before the infection progresses. Heat shock at the site of prodromal symptoms, where HSV has been reactivated, may help increase the immune response to HSV infection.

In response to heat shock, increased amounts of human heat shock proteins (HSPs) such as HSP70, HSP90, and glycoprotein 96 (gp96), are produced [1]. These HSPs find and partner with small protein fragments from inside virally infected cells. Some of these small fragments are from proteins made by the HSV virus. The HSPs deliver the viral protein fragments (antigens) to a protein on the surface of the virally-infected skin cell. This makes these cells targets for killing by the immune system; cells displaying viral antigens on their surface are recognized by a type of white blood cell called cytotoxic T cells.

The recognition of viral antigens on a cell's surface by the cytotoxic T cells causes the destruction of that cell. This early and rapid elimination of virally-infected cells prevents the virus from spreading between cells. This, in turn, leads to more rapid resolution of the viral outbreak, and a return to the latent phase, which is free of symptoms.

Reference

1. Srivastava, P.K., et al., Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity, 1998. 8(6): p. 657-65.