A single-blind, dose escalation, phase I study of high-fluence light-emitting diode-red light (LED-RL) on human skin: study protocol for a randomized controlled trial

Abstract

BackgroundSkin fibrosis is involved in a variety of pathologic conditions ranging from scar formation secondary to surgery or trauma to immune-mediated processes. Skin fibrosis is a significant international health problem with an estimated incidence of greater than 100 million people affected per year worldwide with few effective treatment options available. Preliminary in vitro data generated by our research group suggests that red light can function as a stand-alone treatment for skin fibrosis. To our knowledge, no prior clinical trials have been performed to determine the safety of high-fluence (dose) light-emitting diode-red light (LED-RL) phototherapy. The goal of this study is to evaluate the safety of LED-RL fluences from 160 J/cm2 up to 640 J/cm2 in healthy subjects.Methods/designThis is a single-blind, dose escalation, randomized controlled, phase I study to evaluate the safety of high-fluence LED-RL on human skin. The protocol for dose escalation requires subjects be enrolled sequentially in groups of five. Within each group, three subjects will be randomized to LED-RL phototherapy and two subjects randomized to mock therapy. Subjects in group 1 randomized to LED-RL phototherapy will receive the maximum recommended starting dose (160 J/cm2). LED-RL dose will be escalated in subsequent groups (320 J/cm2, 480 J/cm2 and 640 J/cm2). The maximally tolerated dose (MTD) is defined as the dose level below the dose producing unacceptable but reversible toxicity and is considered to be the upper limit of subject tolerance. After either a MTD has been established, or the study endpoint of 640 J/cm2 has been achieved, an additional 27 LED-RL phototherapy subjects (for a total of 30) and 18 mock therapy subjects (for a total of 20) (determined randomly) will be enrolled. Each subject will receive a total of nine procedures, three times per week for three consecutive weeks.DiscussionThis study may provide important safety information on the effects of high-fluence LED-RL phototherapy on human skin and help facilitate future phase II studies to evaluate the efficacy of high-fluence LED-RL as a potential noninvasive, safe, portable, at-home therapy for treatment of skin fibrosis.Trial registrationClinicalTrials.gov NCT02630303. Registered on 9 December 2015. Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1518-7) contains supplementary material, which is available to authorized users.

Early cases of acute infectious respiratory syndrome treated with photobiomodulation, diagnosis and intervention: Two case reports

“…14,24 PBMT has also demonstrated a biphasic dose-response described through the Arndt Shultz curve: low power of light having stimulative and high power inhibitory effects resulting in ROS decrease activating NF-kB transcription factors according to cells' redox state. 15,25,26 In a recent case report, IR-PBMT at peak powers 808 nm and 905 nm has enabled the cytokine storm's management in a COVID-19 patient. 12 In the pathophysiology of COVID-19, a non-invasive therapeutic modality able to decrease the IL-1β, IL-6, IL-8, TNFα and MCP-1 proinflammatory cytokines would reduce the fatality rate of the disease.…”

A single-blind, dose-escalation, phase I study of high-fluence light-emitting diode-red light on Caucasian non-Hispanic skin: study protocol for a randomized controlled trial

“…There may be several potential limitations of this study, as previously mentioned [22]. There may be a gender bias toward male subjects recruited within the veteran population since females represent only 9% of veterans nationwide [37].…”

“…As previously described [ 22 ], the study procedure for subjects receiving LED-RL phototherapy and for subjects receiving mock therapy is identical with the exception of using different devices. The subject’s non-dominant proximal volar forearm will be cleaned with 70% isopropyl alcohol prep pads 1 min prior to device placement.…”

“…We previously investigated the safety profile of LED-RL phototherapy at fluences of 160, 320, and 480 J/cm 2 in all skin types in a dose-escalation, phase I RCT (ClinicalTrials.gov Identifier: NCT02630303) (unpublished data). The study protocol was published in Trials [ 22 ]. The maximum recommended starting dose (MRSD) of 160 J/cm 2 was based on maximum LED-RL doses used in previous clinical studies that established safety without adverse events [ 23 , 24 ].…”

Safety of light emitting diode‐red light on human skin: Two randomized controlled trials

“…Two phase I, single‐blind, dose escalation, randomized controlled trials were conducted to evaluate the safety of LED‐RL administered three times weekly, a standard phototherapy regimen, for three consecutive weeks . The complete study protocols are published elsewhere and available for reference . The treatment site was the nondominant proximal volar forearm.…”