Light Emitting Diode-Red Light (LED-RL) Phototherapy for Skin Scarring Prevention

• ClinicalTrials.gov Identifier: NCT03795116
• Recruitment Status: Completed
• First Posted: January 7, 2019
• Results First Posted: June 1, 2022
• Last Update Posted: June 1, 2022
• Sponsor: State University of New York - Downstate Medical Center
• Information provided by (Responsible Party): Jared Jagdeo, MD, MS, State University of New York - Downstate Medical Center

Study Description

Brief Summary:

Skin scarring (fibrosis) is a common complication in the wound healing process and remains a therapeutic challenge. Scar formation often occurs following injury to the skin such as surgery, trauma, and burns. The goal of this study is to evaluate the safety and efficacy of visible red light as a modality to reduce skin scarring after mini-facelift surgery. Based on laboratory data, light emitting diode-red light (LED-RL) phototherapy may lessen post-surgical skin fibrosis clinically.

Condition or disease	Intervention/treatment	Phase
Fibrosis; Skin Scarring; Skin Wound; Hypertrophic Scar; Scar; Keloid	Device: LED-RL phototherapy; Device: Mock irradiation	Phase 2

Detailed Description:

Skin fibrosis is a significant global health problem that has a profoundly negative impact on quality of life. Characterized by excessive fibroblast proliferation and collagen deposition, skin fibrosis underlies a wide spectrum of dermatologic conditions ranging from pathologic scars secondary to injury (e.g., burns, surgery, trauma) to immune-mediated diseases. Effective anti-scarring therapeutics remain an unmet need, underscoring the importance of developing novel approaches to treat and prevent skin fibrosis.

In vitro data show that LED-RL can modulate key cellular and molecular processes involved in skin fibrosis. Two phase I clinical trials (STARS 1 and STARS 2) demonstrated the safety and tolerability of LED-RL at fluences of 160 J/cm2 up to 480 J/cm2 on normal human skin. The administration of LED-RL phototherapy in the early postoperative period may optimize wound healing and prevent excessive scarring. The results from this study may change the current treatment paradigm for fibrotic skin diseases and help to pioneer LED-RL as a safe, non-invasive, cost-effective, portable, at-home therapy for scars.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: This is a single-blind study. Participants and clinicians involved in subjective efficacy assessments will be blind to the study intervention (LED-RL phototherapy versus mock therapy). The principal investigator, along with the research coordinator who administers the LED-RL phototherapy, will be aware of each participant's treatment assignment.
• Primary Purpose: Treatment
• Official Title: Light Emitting Diode-Red Light (LED-RL) Phototherapy for Skin Scarring Prevention
• Actual Study Start Date: March 18, 2019
• Actual Primary Completion Date: October 26, 2020
• Actual Study Completion Date: October 26, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: LED-RL phototherapy; Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week after surgery (postoperative days 4-8), treatments will be administered three times weekly for three consecutive weeks.	Device: LED-RL phototherapy; The LED-RL treatment device has a 4.7 cm x 6.1 cm rectangular array of LEDs and emits visible red light (633 nm) at a power density of 360.2 W/m2 at room temperature and a distance of 10 mm from the target surface.; Other Name: Omnilux handheld LED system (GlobalMed Technologies, Glen Ellen, CA)
Sham Comparator: Mock irradiation; Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week after surgery (postoperative days 4-8), treatments will be administered three times weekly for three consecutive weeks.	Device: Mock irradiation; The mock therapy device is designed to sound, look, and feel identical to the LED-RL treatment device (i.e., has the same physical components and thermal output), except it does not emit visible red light.

Outcome Measures

Primary Outcome Measures :

1. Change in Scar Pliability Between the Treated and Control Incision Sites as Measured by Skin Elasticity at 6 Months Compared to Baseline [ Time Frame: 1 month, 3 months, 6 months ]
   The ElastiMeter, a non-invasive indentation instrument, will be used to evaluate skin elasticity (i.e., skin stiffness) of the LED-RL-treated scar versus the untreated scar. Skin elasticity is measured in Newtons/meters (N/m).
2. Change in Scar Pliability Between the Treated and Control Incision Sites as Measured by Skin Induration at Three Follow-up Time Points Compared to Baseline [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   The SkinFibroMeter, a non-invasive indentation instrument, will be used to evaluate the induration of the skin and subcutaneous tissue (i.e., hardness) of the LED-RL-treated scar versus the untreated scar. Skin induration is measured in Newtons (N).

Secondary Outcome Measures :

1. Observer Scar Assessment Scale [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   The scale consists of six items rated from 1 to 10, where 1 is "normal skin" and 10 is the "worst imaginable scar". The observer (i.e., investigator) evaluates scar vascularity, pigmentation, thickness, relief, pliability, and surface area. The scores of each of the six items are summed for a total score (range 6 to 60).
2. Visual Analog Scale (VAS) Scoring of Digital Photographs of Scars [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   The scar images will be rated by two independent, blinded dermatologists using a VAS. The VAS is presented as a 10 cm horizontal line, where the extreme ends of 0 indicates "normal skin" and 10 corresponds to the "worst possible scar," for each of the following scar attributes: pigmentation, vascularity, observer comfort, contour, and overall severity.
3. Dermal Collagen Concentration [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   A non-invasive, handheld diffuse reflectance probe will be used to measure collagen concentration in the dermis at each incision site. The scale ranges from 10 to 99 and the collagen measurement corresponds to the half of the optical scattering coefficient of the dermis.
4. Dermal Water Concentration [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   A non-invasive, handheld diffuse reflectance probe will be used to measure water concentration in the dermis at each incision site. Infrared light is emitted at different wavelengths to retrieve the scattering and the absorption coefficients of the dermis. The more water, the less reflectance. Concentration ranges from 40% to 85%.
5. 3D Imaging Analysis: Pigmentation of Scar Tissue [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   A 3D digital imaging system will be used to construct 3D images of the scars for colorimetric analyses, including quantitative measurements of pigmentation at each incision site.
6. 3D Imaging Analysis: Vascularity of Scar Tissue [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   A 3D digital imaging system will be used to construct 3D images of the scars for colorimetric analyses, including quantitative measurements of vascularity at each incision site.
7. 3D Imaging Analysis: Volume of Elevation of Scar Tissue [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
   A 3D digital imaging system will be used to construct 3D images of the scars for skin profilometry analyses, including quantitative measurements of tissue volume at each incision site.
8. Histological Analysis: Collagen Content of Scar Tissue (Optional) [ Time Frame: Skin specimens will be obtained via optional 2 mm punch biopsy on post-operative day 0 (prior to surgery) and post-operative day 30 (first follow-up visit after completion of LED-RL treatment). ]
   The histological changes that occur in vivo in response to LED-RL phototherapy will be evaluated by examination of pre- and post-treated skin tissue. Skin specimens will be obtained via optional 2 mm punch biopsy and stained for collagen fibers.
9. Number of Participants Experiencing Adverse Events in Each Treatment Group [ Time Frame: From first LED-RL and mock phototherapy treatment session on post-operative day 5 until final follow-up visit on post-operative day 180 (6 month follow-up). ]
   Subjects will be provided with a daily diary to record any adverse events experienced during the three-week intervention period. Treatment sessions will be monitored closely for the occurrence of any safety issues or adverse events, as reported by the subject or observed by the clinical research team. At each follow up visit, patients will be asked about adverse effects.
10. Patient Scar Assessment Scale [ Time Frame: Baseline assessment was completed on post-operative day 5, before LED-RL or mock phototherapy treatment. Follow-up visits were scheduled on approximately post-operative day 30 (1 month), post-operative 90 (3 months), and post-operative day 180 (6 months). ]
    The scale consists of six items rated from 1 to 10, where 1 is "normal skin" and 10 is the "worst imaginable scar". The patient assesses pain, itching, color, stiffness, thickness, and irregularity. The scores of each of the six items are summed for a total score (range 6 to 60).

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Provision of written informed consent for all study procedures
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Suitable candidate for elective mini-facelift surgery
• Pass a screening photosensitivity test

Exclusion Criteria:

• Current use of any photosensitizing medications
• Light-sensitive conditions
• Diabetes mellitus
• Systemic lupus erythematosus
• Current tobacco use
• History of bleeding or coagulation disorder
• Lax skin associated with genetic disorders
• Open wounds on the face or neck
• Fibrotic skin disease, pre-existing scar(s), or other skin conditions affecting the periauricular skin
• History of surgery or procedure involving or affecting the periauricular skin within the past 6 months (e.g., prior facelift, fillers, laser therapy)
• Tattoos that cover the proposed treatment sites on the periauricular skin
• Any other medical condition(s) that could be compromised by exposure to the proposed treatment

Contacts and Locations

Locations

United States, New York

SUNY Downstate Medical Center

Brooklyn, New York, United States, 11203

Sponsors and Collaborators

State University of New York - Downstate Medical Center

  Study Documents (Full-Text)

Documents provided by Jared Jagdeo, MD, MS, State University of New York - Downstate Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] July 30, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nguyen JK, Weedon J, Jakus J, Heilman E, Isseroff RR, Siegel DM, Jagdeo JR. A dose-ranging, parallel group, split-face, single-blind phase II study of light emitting diode-red light (LED-RL) for skin scarring prevention: study protocol for a randomized controlled trial. Trials. 2019 Jul 15;20(1):432. doi: 10.1186/s13063-019-3546-6.

• Responsible Party: Jared Jagdeo, MD, MS, Associate Professor of Dermatology, State University of New York - Downstate Medical Center
• ClinicalTrials.gov Identifier: NCT03795116
• Other Study ID Numbers: 1304108
• First Posted: January 7, 2019
• Results First Posted: June 1, 2022
• Last Update Posted: June 1, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Jared Jagdeo, MD, MS, State University of New York - Downstate Medical Center:

Light emitting diode; Light emitting diode-red light; Visible red light; Skin fibrosis; Wound healing; Scarring

Additional relevant MeSH terms:

Fibrosis; Cicatrix; Cicatrix, Hypertrophic; Pathologic Processes