Immune Response and General Immune Health in Subjects Infected With Herpes Simplex Virus Type 1 (HSV-1)
Condition: HSV; Herpes Labialis
MeSH terms: Herpes Simplex; Herpes Labialis
Intervention: Squaric Acid Dibutyl Ester
Intervention description: 2% squaric acid dibutyl ester (SADBE) (Supplied by Squarex) is topically applied to the inner aspect of the upper arm of the subject and covered with Tegaderm. Subject is advised to wash it off after 3 hours.
Intervention MeSH terms: Squaric acid dibutyl ester
Phase: Phase 1
Study type: Interventional
Primary purpose: Screening
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1:
x Group A: 12 subjects with 6 or more herpes labialis outbreaks in the past 12 months x Group B: 12 subjects with 1 to 2 outbreaks in the past 12 months x Group C: 12 subjects with zero outbreaks in the past 12 months Subjects in group A will receive 2% SADBE dose on the arm after their initial blood samples are obtained. Group A subjects will have blood collected and tests repeated 2 and 8 weeks later.
Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges.
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Squaric Acid; Squaric acid dibutyl ester; cold sores

Summary:

      Subjects were recruited who were positive for antibody against herpes simplex virus type 1
      (HSV-1) and self-reported having in the previous 12 months

        -  6 or more herpes labialis outbreaks (group A),

        -  1 or 2 outbreaks (group B), or

        -  zero outbreaks (group C). Twelve subjects in each group were recruited. Blood was
           collected from these persons and peripheral blood mononuclear cells (PBMCs) isolated and
           tested for proliferation in vitro when stimulated with HSV-1-infected cell extracts,
           free HSV-1 virus, or Candida albicans extract. Candida albicans is a ubiquitous
           infectious fungus and its extract is used as a test of general immune response. RNA was
           also isolated from the PBMCs after incubation in the three stimuli and expression of 41
           immune-related genes quantified by quantitative real-time PCR. Also serum anti-HSV-1 IgG
           levels were quantified.

      After the blood collection on day 1, the persons in group A (frequent cold sore sufferers)
      were treated with a single topical application of 2% squaric acid dibutyl ester (SADBE) in
      DMSO, applied to the inner aspect of the upper arm. These subjects returned on days 15 and 57
      for blood collection, and their PBMCs were tested again on those dates for proliferation in
      vitro against the same stimuli and for gene expression and for serum anti-HSV-1 IgG levels.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥18 and <65

          2. Positive test for IgG against herpes simplex virus type 1 (HSV-1).

          3. Groups A and B only: Clinical diagnosis of herpes labialis, which may be made at the
             screening visit based on the patient's self-reported history of symptoms. An active
             herpes labialis outbreak at the time of entry into the clinical trial will neither be
             required nor will be an exclusion criteria.

          4. Group A only: Self report having six or more episodes of herpes labialis in the past
             12 months. Subjects will NOT be told that six-or-more episodes in the previous 12
             months is the entry criterion. Subjects will be asked "How many separate episodes of
             cold sores have you had in the previous 12 months?" They will be included if they give
             an answer of six or more and excluded from Group A if they give an answer of five or
             fewer.

          5. Group A only: At least half of the subject's episodes of the previous 12 months should
             be vesicular in nature and at least half preceded by prodromal symptoms.

          6. Group B only: Self report having exactly 1 or 2 episodes of herpes labialis in the
             past 12 months. Subjects will NOT be told that one or two episodes in the previous 12
             months is the entry criterion. Subjects will be asked "How many separate episodes of
             cold sores have you had in the previous 12 months?" They will be included if they give
             an answer of one or two and excluded from Group B if they give a different answer.

          7. Group C only: Self report having zero episodes of herpes labialis in the past 12
             months. Subjects will NOT be told that zero episodes in the previous 12 months is the
             entry criterion. Subjects will be asked "How many separate episodes of cold sores have
             you had in the previous 12 months?" They will be included if they give an answer of
             zero and excluded from Group C if they give an answer of one or more.

        Exclusion Criteria:

          1. Pregnant or lactating females.

          2. Current or recurrent non-herpetic infection or any underlying condition that may
             predispose to infection or anyone who has been admitted to the hospital due to
             bacteremia, pneumonia or any other serious infection in the last 12 months.

          3. Therapy with glucocorticoid or immunosuppressants at time of recruitment or within
             past 4 weeks prior to the screening visit (including inhaled corticosteroids for
             asthma), except for topical steroids in sites other than face.

          4. History of malignancy (except patients with surgically cured basal cell or squamous
             cell skin cancers).

          5. History of organ transplantation.

          6. HIV-positive status determined by history at screening or known history of any other
             immunosuppressive disease.

          7. Severe co-morbidities (diabetes mellitus requiring insulin, CHF (NYHA class II or
             worse) MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris,
             oxygen-dependent severe pulmonary disease

          8. Known hypersensitivity to Dimethyl sulfoxide (DMSO).

          9. Any condition judged by the investigator to cause this clinical trial to be
             detrimental to the patient.

         10. Subject is currently enrolled in another investigational device or drug trial(s), or
             subject has received other investigational agent(s) within 28 days of baseline visit.

         11. Previous exposure to SADBE (squaric acid or squaric acid dibutyl ester).

         12. Subject has an abnormal skin condition (e.g., acne, eczema, rosacea, psoriasis,
             albinism, or chronic vesiculo-bullous disorder) that occurs in the area ordinarily
             affected by herpes labialis.

         13. Subject has had a vaccine for either HSV-1 or HSV-2.

         14. Group A only: People that have had treatment with anti viral therapy within 2 weeks
             before sensitization dose of SADBE.

         15. Groups B and C only: People that have had treatment with anti-viral therapy any time
             in the past 12 months.