Treatment of Herpes Labialis by Photodynamic Therapy

Photodynamic Therapy Clinical Trial

— Herpes  

Official title:

Treatment of Herpes Labialis by Photodynamic Therapy: Controlled, Prospective, Randomized, Double-blind Protocol Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04037475
• Other study ID #: Herpes
• Status: Completed
• Phase: N/A
• Start date: January 1, 2020
• Est. completion date: October 15, 2023

Study information

• Verified date: November 2023
• Source: University of Nove de Julho
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Materials and methods: 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 TCLE and TA, 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. In all patients will be collected saliva samples for analysis of cytokines, and will be performed exfoliative cytology in the lesions. The pain will be assessed through a pain scale and a questionnaire of quality of life-related to oral health (Ohip- 14) will be given to them. Patients will continue to be followed up after 7 days, 1 month, 3 months, 6 months and 1 year and, if there is a recurrence of the lesion, they will contact the researchers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 15, 2023
• Est. primary completion date: October 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients of both sex,

• with no predilection for race or socioeconomic status,

• negative medical history

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Herpes Labialis
• Herpes Simplex
• Herpes Simplex, Labial
• Photodynamic Therapy

Intervention

Device:
• photodynamic therapy herpes labialis
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.

Locations

Country	Name	City	State
Brazil	Anna Carolina R.T. Horliana	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Nove de Julho

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

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. — View Citation

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 carcino — View Citation

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluate if the amount of HSV-1 decreases after treatment with PDT	by qPCR (polymerase reaction ) at the baseline (T0), 3 (T1) and 7 (T2).HSV lesion secretion samples will be collected at 1 single site in the central portion of the lesion with sterile swab after treatment of all HSV lesions. They will be stored in 500 µl of Tris-EDTA (ethylenediamine tetraacetic acid) in tubes of 1 , 5ml for microcentrifuge (Eppendorff®). During the collection period (in the clinic) the samples will be stored on ice inside a styrofoam. These samples will be properly identified and stored at -80ºC (centigrades) (freezer from the UNINOVE University nove de Julho Biophotonics Laboratory) until further analysis.	through study completion on average of three years
Secondary	evaluation of saliva cytokines IL-6, IL-1ß, IL-8, TNF-a (tumor necrosis factor) and IL-10 (interleukine)	by ELISA method in non-stimulated saliva in the baseline (T0), 3 (T1) and 7 T2) and 30 days after treatment (T3).Samples of unstimulated saliva (2 ml) will be collected in 50 ml tubes (Falcon tube). In the laboratory 500 µl of pure saliva will be added to 500 µl TE (tris-EDTA), and stored at -80 ° C (freezer from the UNINOVE Biophotonics laboratory).	through study completion on average of three years
Secondary	presence of pain: visual analog scale	verify the pain by visual analog scale at baseline (T0), 3 (T1) and 7 (T2) and 30 days after treatment (T3).Will be assessed by applying the visual analogue scale (EVA) with a line of 100 mm, with both ends closed. One end has the indication "0" and the other "10" which means respectively no pain and unbearable pain. Instructions for marking will always be given to the patient by the same operator. Each patient will be instructed to mark with a vertical trace the point that best corresponds to the intensity of pain at the time of evaluation	through study completion on average of three years
Secondary	Oral health impact profile (Ohip-14)	This questionnaire is a simplified form of the original OHIP-49 questionnaire, the Ohip-14, and will be used to assess the impact of oral health on the quality of life of the research participants. The Ohip-14 is used to measure perceived needs. It measures the impact of oral changes on oral health related quality of life. The patient responds to 14 questions by assigning to his answers the values 0 (never), 1 (almost never), 2 (sometimes), 3 (most of the time) and 4 (always)	through study completion on average of three years
Secondary	Temperature	The temperature will be measured at the site of the lesion (at its central point) and at its side (healthy skin 2 cm from the edge of the lesion). The local measurement will be measured using the Safety 1st® digital thermometer (Safety 1st®, "No Touch Forehead", Columbus, USA	through study completion on average of three years
Secondary	evaluation of HSL lesions cytokines IL-6, IL-1ß, IL-8, TNF-a (tumor necrosis factor) and IL-10 (interleukine)	by ELISA method in HSL lesions in the baseline (T0), 3 (T1) and 7 T2) and 30 days after treatment (T3).Samples of unstimulated saliva (2 ml) will be collected in 50 ml tubes (Falcon tube). In the laboratory 500 µl of pure saliva will be added to 500 µl TE (tris-EDTA), and stored at -80 ° C (freezer from the UNINOVE Biophotonics laboratory).	through study completion on average of three years