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

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(unpublished data, investigator research group).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).

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"