Phase 1 Study of HF-LED-RL in Fitzpatrick Skin Types I to III

Study Overview
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Brief Summary
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The goal of this study is to establish the safety of high fluence LED-RL at fluence of 480 J/cm2 and 640 J/cm2 in healthy non-Hispanic, Caucasian subjects. The hypothesis is that high fluence LED-RL phototherapy is safe in non-Hispanic, Caucasians.

Detailed Description
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The effects of visible light, while common in the environment (visible spectrum accounts for 44% of total solar energy), remain undefined. An important safety feature of visible red light (600 nm to 700 nm) is that it does not generate pro-carcinogenic DNA damage as does ultraviolet (UV) light. Recently published clinical observations indicate that red light in combination with other modalities such as photosensitizers in combined red light photodynamic therapy can treat skin diseases. However, preliminary in vitro data generated by the investigator's research group suggests that red light can function as a stand-alone treatment, eliminating the side-effects of chemical photosensitizers and the potential long-term harm of current UV therapy. Furthermore, commercially available light emitting diode-red light (LED-RL) units exist and are already FDA-cleared for other dermatological uses (such as rhytides and acne), thus clinical translation for use in skin diseases could occur relatively quickly following safety and efficacy demonstration. Developing high fluence LED-RL phototherapy as a treatment for skin conditions may represent an important advance that lacks the serious systemic side effects associated with immunomodulatory agents (such as oral steroids); avoids the need for invasive, painful injections with anti-fibrotic agents (such as intralesional steroids, 5-fluorouracil and bleomycin); and eliminates the UV-induced DNA damage associated with skin cancer and photoaging that are associated with current UVA/UVA1 and UVB/narrowband UVB phototherapy. To the investigator research group's knowledge, no clinical trials have been performed to determine the safety of high fluence LED-RL in different Fitzpatrick skin types. The innovation of this approach is that the investigator research group intend to study the safety of high fluence LED-RL in Fitzpatrick skin types I to III (based on NIH's race/ethnicity category of non-Hispanic, Caucasian). A previous study demonstrated that fluence up to 320 J/cm2 is safe for all skin types (unpublished data, investigator research group). This study will evaluate doses of 480 J/cm2 and 640 J/cm2 in Fitzpatrick skin types I to III. This is based on the classical method for dose escalation as described by Spilker: starting with dose (X) increased by an equal amount (in this instance: X=160 J/cm2 which is the maximum recommended starting dose in clinical studies, 2X=320 J/cm2, 3X=480 J/cm2, 4X=640 J/cm2).

Official Title
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EBIRE: Phase 1 Study of High Fluence LED-Red Light in Fitzpatrick Skin Types I to III

Conditions
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Skin Diseases, Keloid, Scar, Fibrosis, Hypertrophic Skin

Intervention / Treatment
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* Device: HF-LED-RL Phototherapy
* Device: Mock Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects of any sex and age Non-Hispanic, Caucasian race/ethnicity Nondominant proximal anterior forearm is wide enough to ensure reproducible placement of LED-RL phototherapy or mock therapy hand-held unit Available and willing to attend all clinic visits Able and willing to give informed consent Exclusion Criteria: Subjects using any photosensitizers (i.e. lithium, melatonin, phenothiazine antipsychotics, antibiotics) Subjects with diabetes mellitus (DM) Subjects with a history of skin cancer. Subjects with systemic lupus erythematous (SLE) Subjects with light-sensitive conditions (All subjects will be tested for photosensitivity per manufacturer user guide instructions) Subjects with open wounds on the nondominant proximal anterior forearm Subjects with fibrotic skin disease or other skin conditions on the nondominant proximal anterior forearm Subjects with tattoos that cover the procedure site on the nondominant proximal anterior forearm Subjects of an ethnic race group other than Non-Hispanic, Caucasian Subjects who have previously participated in the VA Northern California's Phase 1 Study of LED-RL in Human Skin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-blind, dose escalation, randomized controlled Phase 1 study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HF-LED-RL Phototherapy<br>The protocol for dose escalation requires subjects be enrolled sequentially in groups of five (three subjects randomized to HF-LED-RL phototherapy and two subjects randomized to mock therapy). After either a maximally tolerated dose (MTD) has been established or the study endpoint of 640 J/cm2 has been achieved, an additional 24 or 27 HF-LED-RL phototherapy subjects (for a total of 30) and 16 or 18 mock therapy subjects (for a total of 20) (determined randomly) will be enrolled to satisfy Hanley's Rule of Three, such that it can be concluded with 95% confidence that fewer than 1 person in 10 will experience an adverse event. | Device: HF-LED-RL Phototherapy<br>* The starting dose of 480 J/cm2 will be administered to Group 1's HF-LED-RL phototherapy randomized subjects and the HF-LED-RL dose will be escalated in the subsequent group to 640 J/cm2. Common expected procedure side effects are mild and temporary, including warmth, redness (erythema) and swelling (edema). The maximally tolerated dose (MTD) is defined as the dose level below the dose producing unacceptable but reversible toxicity in 2 or more subjects and is considered the upper limit of subject tolerance. All subjects will receive total of nine LED-RL phototherapy, three times per week for three consecutive weeks.<br>* Other names: Omnilux New-U (Photo Therapeutics, Carlsbad, CA);|
| Sham Comparator: Mock Therapy<br>The protocol for dose escalation requires subjects be enrolled sequentially in groups of five (three subjects randomized to HF-LED-RL phototherapy and two subjects randomized to mock therapy). After either a maximally tolerated dose (MTD) has been established or the study endpoint of 640 J/cm2 has been achieved, an additional 24 or 27 HF-LED-RL phototherapy subjects (for a total of 30) and 16 or 18 mock therapy subjects (for a total of 20) (determined randomly) will be enrolled to satisfy Hanley's Rule of Three, such that it can be concluded with 95% confidence that fewer than 1 person in 10 will experience an adverse event. | Device: Mock Therapy<br>* Mock therapy will be administered to mock therapy randomized subjects using the mock therapy unit. The mock therapy unit only generates warmth and does not emit LED-RL. All subjects will receive total of nine mock therapy procedures, three times per week for three consecutive weeks.<br>* Other names: Mock therapy unit (Photo Therapeutics, Carlsbad, CA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | The primary objective is to determine the maximum tolerated dose. | 3 consecutive weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety profile by evaluating incidence of procedure-related common procedure outcomes | To evaluate safety of high fluence LED-RL phototherapy by recording any common expected procedure outcomes [warmth, erythema (redness), and edema (swelling) that are mild, self-limited, and are expected to last less than 24 hours] via assessment during and immediately post-procedure and subject diary of adverse events. | 3 consecutive weeks | 
| Assessment of safety profile by evaluating incidence of adverse events | To evaluate safety of high fluence LED-RL phototherapy by recording adverse events (including: first-degree or higher skin burning or blistering, erythema lasting more than 24 hours, severe swelling, pain, ulceration, change in sensation, and/or muscle weakness], via assessment during and immediately post-procedure and subject diary of adverse events. | 3 consecutive weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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light emitting diode-red light, high fluence, red light, RCT