Treatment of Herpes Labialis by Photodynamic Therapy

NCT04037475 | Completed

• 1 other identifier: Herpes
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Lesions of herpes labialis are caused by the herpes simplex virus type 1 (HSV-1) and cause pain and aesthetic compromise. It is characterized by the formation of small vesicles that coalesce and rupture forming extremely painful ulcers, that evolve to crusts, dry desquamations until their complete remission. Currently, the treatment of these lesions is done with acyclovir. Although it diminishes the symptomatology, it causes viral resistance and does not prevent the recurrence of the lesions. It is known that photodynamic therapy (PDT) has numerous advantages, among them: the reduction of the time of remission, and does not cause resistance. A total of 30 patients with herpes labialis in the prodromal stage of vesicles, ulcers, and crusts will be selected to participate in the study and randomized into two groups: G1 control and G2 experimental. After signing informed consent, patients in group G1 will undergo the standard gold treatment for cold sores with acyclovir and simulated PDT treatment. Patients in the experimental G2 group will be treated simulating the gold standard treatment of herpes labialis (placebo) and PDT.

Conditions

Photodynamic Therapy; Herpes Simplex, Labial

Keywords

photodynamic therapy; herpes labialis; herpes simplex; laser

Outcome Measures

Primary Outcomes (1)

• Evaluation of the resolution time of the lesions

  Evaluation of the resolution time of the lesions in days (primary objective of the study). For this, a 15-day follow-up will be performed for this variable.The complete resolution will be accompanied by photos and telephone contact and noted in a specific clinical file. For this, a 1-year follow-up will be performed for this variable. The location of the lesions through sextants on the lips (sextants 1, 2 and 3 to upper left to right and sextants 4,5 and 6 from right to left, with sextant 2 in the labial filter region and sextant 5 is its lower lip antagonist.

  through study completion on average of one year

Secondary Outcomes (6)

• Evaluate if the amount of HSV-1 decreases after treatment with PDT

  through study completion on average of three years

• evaluation of saliva cytokines IL-6, IL-1β, IL-8, TNF-α (tumor necrosis factor) and IL-10 (interleukine)

  through study completion on average of three years

• presence of pain: visual analog scale

  through study completion on average of three years

• Oral health impact profile (Ohip-14)

  through study completion on average of three years

• Temperature

  through study completion on average of three years

Study Arms (2)

Control (placebo)

PLACEBO COMPARATOR

The patients will receive an agent with the same vehicle as methylene blue to mimic irrigation with the photosensitizer and the laser will be switched off at the time of application. The placebo PDT procedures will be performed on the lesion: Application of methylene blue placebo with a carpule syringe and needle (with stop and without bevel) inside the lesions; 1 minute of pre-irradiation will be expected. The irradiations will be performed with the same device positioned in the same way and at the same time of application, however, the laser will be turned off. The beep sound will be recorded and turned on during application to blind treatment to the patient. The patient will receive a catheter with acyclovir cream and will be advised to spread on the lesions four times a day for 7 days, which will be their return for reevaluation. It will be washed in abundance with saline (saline solution) until the total removal of the placebo from the photosensitizer.

Device: photodynamic therapy herpes labialis

experimental group

EXPERIMENTAL

Patients will be treated with photodynamic therapy and will receive a placebo ointment simulating acyclovir cream. If the lesions are in the vesicle phase, they will be ruptured with a sterile needle. The methylene blue solution at 0.005% concentration will be gently placed on the lesions. Application of methylene blue on the lesions.1 minute of pre-irradiation will be expected. The irradiations will be performed with the Laser Duo® with a wavelength of 660 nm, with a power of 100 mW(milliwatts), the energy density of 300 J / cm², with the energy of 3 J (joules) in the center of the lesion for 30 seconds. The laser will be positioned in direct contact with the lesion, perpendicular, applied centrally to each lesion with energy per point of 3J. Wash in abundance with saline solution until the removal of the photosensitizer is complete. Patients will receive a tube with a placebo cream simulating aciclovir and the same will be advised to spread the cream 4 times per day for 7 days.

Device: photodynamic therapy herpes labialis

Interventions

photodynamic therapy herpes labialis DEVICE

Patients will receive Photodynamic Therapy (PDT), irradiations will be performed with the Laser Duo® red laser diode (MMOptics, São Carlos, SP, Brazil) with a wavelength of 660 nm, with a power of 100 mW, the energy density of 300 J / cm², with energy of 3 J in the center of the lesion for 30 seconds. The laser will be positioned in direct contact with the lesion, perpendicular, applied centrally to each isolated lesion that presents with fixed energy per point of 3J. Wash in abundance with saline solution until the removal of the photosensitizer is complete. All treatment proposed in group 1 (simulation of PDT + delivery of aciclovir cream) in each patient will be concluded in a single session. Treatment for group 2 (PDT + placebo cream) will also be completed in a single session. All possible adverse effects will be noted and qualified during the treatment protocol and maintenance period (3/3 months) using the questionnaire developed for this protocol.

Control (placebo); experimental group

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \- Patients of both sex,
• with no predilection for race or socioeconomic status,
• negative medical history

You may not qualify if:

• Patients with a herpes infection in the dry desquamation stage will be excluded.
• Participants in continuous use of non-steroidal anti-inflammatory drugs and continued corticosteroid therapy for less than 1 week.
• Diabetic participants, smokers
• who need immunosuppressants,
• pregnant women and/or nursing mothers.
• HIV positive,
• hepatitis B or C.

Sponsors & Collaborators

• University of Nove de Julho: lead

Study Sites (1)

Anna Carolina R.T. Horliana

São Paulo, São Paulo, 11030-480, Brazil

Location

Related Publications (5)

• Ramalho KM, Rocha RG, Correa-Aranha AC, Cunha SR, Simoes A, Campos L, Eduardo Cde P. Treatment of herpes simplex labialis in macule and vesicle phases with photodynamic therapy. Report of two cases. Photodiagnosis Photodyn Ther. 2015 Jun;12(2):321-3. doi: 10.1016/j.pdpdt.2015.02.005. Epub 2015 Mar 10. No abstract available.

  PMID: 25770054 RESULT

• Marotti J, Aranha AC, Eduardo Cde P, Ribeiro MS. Photodynamic therapy can be effective as a treatment for herpes simplex labialis. Photomed Laser Surg. 2009 Apr;27(2):357-63. doi: 10.1089/pho.2008.2268.

  PMID: 19382840 RESULT

• Palmieri M, Ornaghi M, Martins VAO, Correa L, Brandao TB, Ribeiro ACDP, Sumita LM, Tozetto-Mendoza TR, Pannuti CS, Braz-Silva PH. Oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy for head and neck squamous cell carcinoma is not affected by xerostomia. J Oral Microbiol. 2018 May 28;10(1):1476643. doi: 10.1080/20002297.2018.1476643. eCollection 2018.

  PMID: 29868164 RESULT

• La Selva A, Bezerra DT, Zerbinati RM, Goncalves MLL, Navarro RS, Bello-Silva MS, Ando-Suguimoto ES, Aranha ACC, Braz-Silva PH, Ramalho KM, Motta LJ, Fernandes KPS, Bussadori SK, Mesquita-Ferrari RA, Frochot C, Horliana ACRT. Herpes Simplex Treated With Antimicrobial Photodynamic Therapy: Randomized Controlled Trial. J Oral Pathol Med. 2025 Aug;54(7):547-555. doi: 10.1111/jop.13647. Epub 2025 Jun 8.

  PMID: 40485092 DERIVED

• La Selva A, Negreiros RM, Bezerra DT, Rosa EP, Pavesi VCS, Navarro RS, Bello-Silva MS, Ramalho KM, Aranha ACC, Braz-Silva PH, Fernandes KPS, Bussadori SK, Horliana ACRT. Treatment of herpes labialis by photodynamic therapy: Study protocol clinical trial (SPIRIT compliant). Medicine (Baltimore). 2020 Mar;99(12):e19500. doi: 10.1097/MD.0000000000019500.

  PMID: 32195950 DERIVED

MeSH Terms

Conditions

Herpes Labialis; Herpes Simplex

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Lip Diseases; Mouth Diseases; Stomatognathic Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Only the researcher responsible for performing the treatments (which will open the envelopes of the randomization) will know which treatment was assigned to each patient. The identification of each group will be revealed only after the statistical analysis of the data for all those involved in the study by this researcher. Therefore, the researcher responsible for data collection, the microbiologist and the statistician will be blind regarding the treatments assigned to the groups. The patient will also be blind to the type of treatment performed, since the treatment of the lesion will be identical in both groups and the treatment with PDT will be simulated in the control group. Aciclovir placebo will be used in the experimental group, so the patient will not know which treatment will be effective.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Postgraduate program professor

Model Details: 24 individuals will be randomly divided into 2 groups: G1 (control group) - conventional treatment with acyclovir and simulation of treatment with photodynamic therapy; G2 (experimental group) - photodynamic therapy placebo ointment simulating acyclovir cream.

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: July 30, 2019
• Study Start: January 1, 2020
• Primary Completion: October 30, 2022
• Study Completion: October 15, 2023
• Last Updated: November 21, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)