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

Abstract

Background: Visible light (400 to 700 nm) is common in our environment, comprising 44% of total solar radiation and a large component of environmental light exposure. The effects of visible light on skin remain undefined. The red light portion of the visible spectrum (600 to 700 nm) may be used to treat skin diseases as a monotherapeutic modality or in combination with other agents. Light-emitting diode-red light (LED-RL) phototherapy may represent an important advance in light-based treatment modalities because it is non-invasive, inexpensive, portable, and easily combinable with other therapies. We previously determined the maximum tolerated dose (MTD) of high-fluence LED-RL (HF-LED-RL) in skin of color individuals to be 320 J/cm2. To the best of our knowledge, no clinical trials have been performed to determine the safety of higher doses of HF-LED-RL in Caucasian non-Hispanic individuals. The aim of this study is to investigate the safety of HF-LED-RL at doses of 480 and 640 J/cm2 in healthy Caucasian non-Hispanic individuals.

Methods: This is a single-blind, dose-escalation, randomized, controlled, phase I trial titled Safety Trial Assessing Red-light on Skin (STARS) 2. Healthy subjects will be randomly assigned to groups of five (three subjects randomly assigned to HF-LED-RL phototherapy and two subjects randomly assigned to mock therapy). Subjects in group 1 will receive HF-LED-RL or mock irradiation at the starting dose of 480 J/cm2, and the dose will be escalated in the subsequent group (group 2) to 640 J/cm2. The MTD is defined as the dose level below the dose at which two or more subjects (>20% of the cohort) experience a dose-limiting toxicity (DLT). After either the MTD is established or the study endpoint of 640 J/cm2 is achieved, additional HF-LED-RL phototherapy subjects and mock therapy subjects will be enrolled at that fluence (group 3) for a total number of up to 60 subjects. Each subject will receive a total of nine irradiation sessions, three times per week for three consecutive weeks.

Discussion: This follow-up study aims to provide important knowledge about safety and cutaneous effects of HF-LED-RL phototherapy of 480 and 640 J/cm2 in Caucasian non-Hispanic subjects. The importance of this clinical trial is that it may establish new treatment paradigms and a safety profile for LED-RL based on race and ethnicity.

Trial registration: ClinicalTrials.gov Identifier: NCT03433222 . Registered on February 1, 2018 - Retrospectively registered. Protocol date and version: January 12, 2018; version 1.

Keywords: Dose escalation; High fluence; Light-emitting diode-red light; Phase I; Phototherapy; Randomized controlled trial; Safety; Study protocol; Visible red light.

Conflict of interest statement

Ethics approval and consent to participate

Study approval was obtained from the Institutional Review Board (IRB) Human Studies Subcommittee at the Sacramento VA Medical Center (reference [18]–01-00804) on January 26, 2018. Any protocol amendments will require IRB approval. Routine auditing of this study will be performed in accordance with VA guidelines. The protocol identification number on ClinicalTrials.gov is NCT03433222. This study will be conducted in accordance with medical professional codex and the Helsinki Declaration as of 1996 as well as Data Security Laws and Good Clinical Practice criteria. Written IRB-approved informed consent will be obtained from all subjects prior to enrollment, and subjects will be given adequate time to declare whether they wish to participate in this study before signing the consent form. Study participation is voluntary and can be withdrawn at any time without provision of reason and without negative consequences for future medical care.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Study dose-escalation flow diagram. The maximum tolerated dose (MTD) is defined as the dose level below the dose producing a dose-limiting toxicity in two or more subjects. Abbreviations: AE adverse event, HF-LED-RL High-fluence light-emitting diode-red light, VA Veterans Affairs.

Fig. 2

Subject diary template to capture patient-reported outcome

Fig. 3

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure. Time schedule of enrollment, interventions, and assessments