- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04037475
Treatment of Herpes Labialis by Photodynamic Therapy (Herpes)
Treatment of Herpes Labialis by Photodynamic Therapy: Controlled, Prospective, Randomized, Double-blind Protocol Study
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Anna Carolina R Horliana, PhD
- Phone Number: 5513981999848 +5513981999848
- Email: annacrth@gmail.com
Study Contact Backup
- Name: Renata Matalon, PhD
- Email: annacrth@gmail.com
Study Locations
-
-
SP
-
São Paulo, SP, Brazil, 11030-480
- Anna Carolina R.T. Horliana
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Control (placebo)
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.
|
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.
|
Experimental: experimental group
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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation of the resolution time of the lesions
Time Frame: through study completion on average of one year
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate if the amount of HSV-1 decreases after treatment with PDT
Time Frame: through study completion on average of three years
|
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
|
evaluation of saliva cytokines IL-6, IL-1β, IL-8, TNF-α (tumor necrosis factor) and IL-10 (interleukine)
Time Frame: through study completion on average of three years
|
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
|
presence of pain: visual analog scale
Time Frame: through study completion on average of three years
|
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
|
Oral health impact profile (Ohip-14)
Time Frame: through study completion on average of three years
|
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
|
Temperature
Time Frame: through study completion on average of three years
|
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
|
evaluation of HSL lesions cytokines IL-6, IL-1β, IL-8, TNF-α (tumor necrosis factor) and IL-10 (interleukine)
Time Frame: through study completion on average of three years
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Anna Carolina R Horliana, PhD, University of Nove de Julho
Publications and helpful links
General Publications
- 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.
- 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.
- 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. Erratum In: J Oral Microbiol. 2021 Mar 29;12(1):1890442.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Herpes
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Photodynamic Therapy
-
Mansoura UniversityEnrolling by invitationPhotodynamic TherapyEgypt
-
Wright State UniversityWithdrawn
-
Bispebjerg HospitalCompletedPhotodynamic Therapy | Ablative Fractional LaserDenmark
-
Clinuvel Pharmaceuticals LimitedCompletedPatients Undergoing Photodynamic Therapy Using Porfimer Sodium
-
Abramson Cancer Center at Penn MedicineRecruitingPatients With Pathologically Confirmed Neoplasia That Have Been | Selected for Definitive Photodynamic Therapy, Proton, or Photon Radiation TherapyUnited States
-
Peking University People's HospitalRecruitingCentral Serous Chorioretinopathy | Therapy, PhotodynamicChina
-
Kafrelsheikh UniversityRecruitingPeriodontal Diseases | Photodynamic Therapy | SimvastatinEgypt
-
Aristotle University Of ThessalonikiUniversity of HelsinkiRecruitingPeriodontitis | Smoking, Cigarette | Non-surgical Periodontal Therapy | Dual- Light Photodynamic TherapyGreece
-
Xiyuan Hospital of China Academy of Chinese Medical...RecruitingAcne | Photodynamic TherapyChina
-
Wright State UniversityCompletedActinic Keratosis | Photodynamic TherapyUnited States
Clinical Trials on photodynamic therapy herpes labialis
-
Centre Hospitalier Universitaire de NiceWithdrawnDystrophic Epidermolysis BullosaFrance
-
Northwestern UniversityCompleted
-
Bispebjerg HospitalCompletedActinic KeratosesDenmark
-
Bispebjerg HospitalCompleted
-
National Taiwan University HospitalCompleted
-
photonamic GmbH & Co. KGCompletedActinic KeratosisGermany
-
University of KansasDUSA Pharmaceuticals, Inc.CompletedHidradenitis SuppurativaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)CompletedRecurrent Non-small Cell Lung Cancer | Stage 0 Non-small Cell Lung Cancer | Squamous Cell Lung Cancer | Adenocarcinoma of the Lung | Large Cell Lung CancerUnited States
-
Fujian Longhua Pharmaceutical Co. LtdSun Yat-sen University; Fuzhou UniversityUnknownEsophageal Cancer | Skin CancerChina
-
University of Sao PauloFundação de Amparo à Pesquisa do Estado de São PauloCompletedAggressive PeriodontitisBrazil