Effect of combined photodynamic therapy and photobiomodulation therapy in the management of recurrent herpes labialis

ISRCTN	ISRCTN10142572
DOI	https://doi.org/10.1186/ISRCTN10142572
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	Nil known
Sponsor	Damascus University
Funder	Damascus University

Submission date: 18/01/2025
Registration date: 20/01/2025
Last edited: 20/01/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Recurrent herpes labialis (RHL) is a common viral infection in the oral and facial areas. RHL is primarily caused by herpes simplex virus type 1 (HSV1). RHL is a global health problem, occurring in approximately 20 to 40% of young adults. RHL lesions are caused by physical and emotional stress, trauma, ultraviolet light, hormonal changes, and immunosuppression. This study aimed to compare Photodynamic therapy (PDT) combined with Photobiomodulation therapy (PBMT) and PBMT using a laser diode and acyclovir cream for treating RHL lesions by analyzing pain and healing parameters.

Who can participate?
Patients aged 19-50 years with RHL lesions.

What does the study involve?
Patients are randomly divided into three groups:
Group 1 (control): 5% Acyclovir was applied as a topical cream, and a non-activating laser was applied.
Group 2 (PBMT): PBMT was applied using a laser diode and a placebo cream.
Group 3 (PDT + PBMT): PDT using methylene blue with PBMT and a placebo cream.

What are the possible benefits and risks of participating?
Benefits: Participants will receive treatment for RHL.
Risks: There is a risk of an ineffective treatment.

Where is the study run from?
Damascus University (Syria)

When is the study starting and how long is it expected to run for?
June 2024 to January 2025

Who is funding the study?
Damascus University (Syria)

Who is the main contact?
Dr Mawia Karkoutly, mawia95.karkoutly@damascusuniversity.edu.sy, mawiamaherkarkoutly@hotmail.com

Contact information

Dr Mawia Karkoutly
Public, Scientific, Principal investigator

Mazzeh
Damascus
Nill
Syria

ORCID ID	0000-0003-0227-1560
Phone	+963 (0)992 647 528
Email	mawia95.karkoutly@damascusuniversity.edu.sy

Study information

Primary study design	Interventional
Study design	Double-blinded randomized parallel-group active-controlled trial with three treatment arms
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effect of combined photodynamic therapy and photobiomodulation therapy in the management of recurrent herpes labialis: a randomized controlled trial
Study objectives	Combining PDT and PBMT in treating RHL lesions will enhance treatment results
Ethics approval(s)	Approved 13/05/2024, The Biomedical Research Ethics Committee (Mazzeh, Damascus, -, Syria; +963 (11) 33923223; dean.dent@damascusuniversity.edu.sy), ref: N2183
Health condition(s) or problem(s) studied	Recurrent herpes labialis
Intervention	Patients referred to the Department of Oral Medicine were evaluated for eligibility. From a total of 73 patients, 60 were randomly assigned into three groups (n = 20): • Group 1 (control): 5% Acyclovir was applied as a topical cream (Veramed, Medico Labs., Damascus, Syria), and a non-activating laser was applied. • Group 2 (PBMT): PBMT was applied using a laser diode and a placebo cream. • Group 3 (PDT + PBMT): PDT using methylene blue with PBMT and a placebo cream. In the control group, a 5% acyclovir cream was administered to the lesion five times a day over 5 days. A non-activating laser was also used on the lesion to ensure blinding. In the PBMT group, a laser diode emitting light at a wavelength of 650 nm and a power output of 100 mW was applied to each spot for 120 seconds. The laser diode treatment was carried out on the first day and again 48 hours after the initial application. In addition, the patient received a package including a placebo cream to be applied five times daily. In the PDT + PBMT group, the area was treated using a cotton ball dipped in sterile saline (SODIUM CHLORIDE 0.9% MIAMED, Miamed Pharmaceutical Industry, Damascus, Syria). A sterile needle tip punctured the vesicle to facilitate the drainage of its contents. The area was dried with sterile gauze within the lesion's borders, avoiding pressure or traction. The herpetic lesion was treated with a 0.01% methylene blue photosensitizer (Citrate Methylene Blue, 0.01% (w/v) 50mL, White labs., California, United States). After five minutes, the LLLT was applied. Any remaining traces of the photosensitizer were removed with a cotton ball soaked in sterile saline, again without pressure or traction. In addition, the LLLT, without the photosensitizer, was utilized 48 hours after the PDT, and the patient was provided with a placebo cream for application five times a day.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	1. Pain intensity Pain intensity was measured using a visual analog scale (VAS), at the following time points: • At the baseline (t0). • After applying the laser in the first session (t1). • Before applying the laser in the second session, after 48 hours (t2). • After applying the laser in the second session (t3). • After 7 days of follow-up (t4). VAS scores were as follows: • 0 = No pain. • 1–3 = Mild pain. • 4–6 = Moderate pain. • 7–9 = Severe pain. • 10 = Worst pain possible. 2. Lesion healing The point of healing was considered to be the spontaneous shedding of the crust from the lesion. Patients were followed up, and the day the crust fell off spontaneously was recorded.
Key secondary outcome measure(s)	There are no secondary outcome measures
Completion date	04/01/2025

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	19 Years
Upper age limit	50 Years
Sex	All
Target sample size at registration	60
Total final enrolment	60
Key inclusion criteria	1. Healthy participants. 2. Participants older than 18 years. 3. Participants had a history of RHL. 4. Participants had a current active vesicular infection.
Key exclusion criteria	1. Smokers. 2. Pregnant and breastfeeding women. 3. Diabetic patients. 4. Immunocompromised patients. 5. Participants were allergic to the agents used. 6. Patients had skin lesions that affected the course of healing or interfered with the current study. 7. Patients taking antiviral medications over the four weeks before treatment. 8. Patients taking anti-inflammatory drugs or antibiotics over the two weeks before treatment.
Date of first enrolment	02/06/2024
Date of final enrolment	06/12/2024

Locations

Countries of recruitment

Syria

Study participating centre

Damascus University

Mazzeh highway
Damascus
-
Syria

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available upon request from Dr Mawia Karkoutly (Mawiamaherkarkoutly@hotmail.com). The type of data that will be shared includes anonymised demographic information that will be available after publication. Consent from participants was required and obtained.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

20/01/2025: Trial's existence confirmed by Damascus University.