Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

Primary oral infection with the herpes simplex virus (HSV) typically occurs at a young age, is asymptomatic, and is not associated with significant morbidity. After primary oral infection, HSV may persist in a latent state in the trigeminal ganglion and later reactivate as the more common herpes labialis, or "cold sores." Common triggers for reactivation are well known and include ultraviolet light, trauma, fatigue, stress, fever, inflammation, and menstruation. These lesions affect up to 45 percent of the U.S. population. They classically manifest as a well-localized cluster of small vesicles along the vermilion border of the lip or adjacent skin. The vesicles subsequently rupture, ulcerate, and crust within 24 to 48 hours. Spontaneous healing occurs over seven to 10 days. In immunocompetent patients, herpes labialis usually is mild and self-limited. However, pain, swelling, and cosmetic concerns may prompt physician consultation. Orally administered antiviral agents, such as acyclovir (Zovirax) or valacyclovir (Valtrex), have a modest clinical benefit if initiated during the prodrome. Topical treatment with 1% penciclovir cream (Denavir) may reduce healing time and pain slightly, even if initiated after the prodrome. However, reduction in healing time with systemic or topical agents is modest. Squaric acid dibutyl ester (SADBE) is a topical immunotherapeutic agent used in the treatment of verruca vulgaris and alopecia areata. During a recent FDA Compounding Advisory Committee Meeting, it was recommended that squaric acid dibutylester be included on the list of bulk drug substances allowed for use in compounding under section 503A of the Federal Food, Drug, and Cosmetic Act. And SADBE has now been so listed under section 503A. A study completed by Lee et al of 29 patients with recalcitrant warts demonstrated complete clearance in 69% of patients with application every 2-4 weeks. Silverberg et al showed a complete clearance in 58% of patients (n=61) when SADBE was applied 3 times weekly. SADBE has also been used with some success in the treatment of alopecia areata. In a review of the literature, Rokhsar et al noted a 50% to 60% success rate of SADBE in use for hair re-growth in this population. SADBE has been reported to cause eczema, lymphadenopathy, blistering, allergic contact dermatitis, skin hypopigmentation, a burning sensation after application, and systemic reactions including fever and arthralgias. A study completed by Oglio et al of eight patients treated with SADBE for warts noted only mild and well tolerated side effects of erythema, desquamation, cutaneous edema, pruritus, burning, and pain. SADBE induces a delayed-type hypersensitivity response which in warts, is believed to induce the killing of virally infected cells by cytotoxic lymphocytes. This influx of lymphocytes into lesional Page 4 of 14 tissue may also enhance the recognition and processing of viral antigens, leading to clonal expansion of effector cells. It is hoped that SADBE will offer subjects a safe and effective therapeutic option to decrease the frequency and severity of future herpes labialis outbreaks through these mechanisms. A placebo-controlled clinical study completed at Massachusetts General Hospital showed that squaric acid prevented recurrence of herpetic lesions. The effect of SADBE of delaying new herpes labialis outbreaks was highly significant (p<0.01) as compared to placebo. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03661541
Study type Interventional
Source Squarex, LLC
Contact
Status Completed
Phase Phase 1
Start date March 2, 2017
Completion date October 25, 2017

See also
  Status Clinical Trial Phase
Completed NCT02483182 - Safety, Tolerability and Therapeutic Efficacy of Topical ZEP-3 Ointment (1.0%) for the Treatment of Cold Sores Phase 2
Completed NCT00297011 - Valacyclovir+Temovate Gel for the Treatment of Herpes Labialis Phase 2
Completed NCT03310294 - Immune Evidence to the Consumption of Lactobacillus GG and FOS Consumption in Patients With Herpes Labialis N/A
Terminated NCT04539483 - Monoclonal Antibody Therapy Against Chronic Herpes Simplex Virus 1 Infection Phase 2
Completed NCT02265913 - Comparative Safety and Efficacy of Two Antiviral Treatments in the Treatment of Recurrent Herpes Simplex Labialis Phase 3
Completed NCT01971385 - Safety and Efficacy of Squaric Acid Dibutyl Ester for the Treatment of Herpes Labialis Phase 1
Active, not recruiting NCT01695187 - NB-001 Treatment of Recurrent Herpes Labialis Phase 3
Completed NCT00375570 - Safety Study of ME-609 for Treatment of Herpes Simplex Labialis in Adolescents Phase 3
Completed NCT02871492 - Trial on Efficacy and Safety of Pritelivir Ointment for Treatment of Labial Herpes Phase 2
Completed NCT01484067 - Study of a Cold Sore Patch for the Treatment of Herpes Labialis N/A
Completed NCT00769314 - Phase 3 Clinical Study for the Treatment of Cold Sore Phase 3
Completed NCT00878072 - Safety and Pharmacokinetics of Famciclovir Single 1500 mg Dose in Adolescents With Recurrent Herpes Labialis Phase 2/Phase 3
Completed NCT01574612 - Open Label Safety Study of Xerese Cream in the Treatment of Recurrent Herpes Labialis in Children 6-11 Years Old Phase 3
Recruiting NCT01306084 - Viral Infections in Healthy and Immunocompromised Hosts
Terminated NCT03521479 - A Phase 2, Muti-Center Study of Repeat Dosing of Squaric Acid Dibutyl Ester in Subjects With Herpes Labialis Phase 2
Terminated NCT00913692 - A Randomized Double-Blind Control-Comparison Crossover Trial of Oral Glutamine to Suppress Frequently Recurrent Herpes Labialis Phase 2
Completed NCT02207881 - A Double-Blind, Randomized, Placebo-Controlled Study of Topical VDO for the Treatment of Herpes Simplex Labialis Phase 2
Completed NCT01653509 - An Exploratory Study to Investigate the Inflammatory Response During a Cold Sore Episode Phase 1
Completed NCT00361881 - Efficacy and Safety Study of ME-609 and Acyclovir for Treatment of Herpes Simplex Labialis Phase 3
Recruiting NCT02582086 - Study of a New Topical Natural Health Product for the Treatment of Herpes Labialis N/A