Wound Healing Endpoint and Recurrence

This prospective pilot study is to enroll patients with clinically-defined infected wounds.
Patients enrolled in the study will be followed for 16 weeks for wound closure (Phase A), and
will then begin Phase B. Wounds will be subjected to Standard of Care (SoC) followed by all
Comprehensive Wound Center (CWC) wound physicians in the first 16 weeks. Trans - Epidermal
Water Loss (TEWL) will be measured with a handheld, non-invasive device, the VapoMeter®
Closed-Chambered device or using DermaLab TEWL probe. Both of these devices are used to read
the device. They will be placed on the subjects skin and will read the TEWL measurement. When
the device is placed on the skin, the measurement takes between 7-20 seconds with the
standard adapter. Study visit 1 will include informed consent being signed, baseline
information collected, 2 biopsies will be collected unless the wound is not appropriate for
biopsy or the patient chooses not to receive a biopsy then a swab for culture will be
collected, wound image, and a quality of life survey will be completed by the subject. The
patients medical chart will be followed for 16 weeks following visit 1. At 16 weeks (+/- 1
week) or within 10 days of wound closure whichever comes first, all subjects will return for
study visit 2. If the target wound(s) is not yet healed at this visit, this visit will be
part of their Standard of Care visit per the CWC. The patient's study participation will end
at this visit but wound data will be collected, digital imaging of wound(s) and quality of
life survey will be completed by the subject. If the target wound is determined by visual
inspection to be healed at or prior to this visit, this will be a research only visit; the
patient will continue to Phase B. Phase B is a continuation of study visit 2. Various
information will be collected on the data collection sheet, digital imaging and TEWL
measurements will be recorded. The TEWL device will be placed on the skin. There will be 5
measurements obtained over the closed wound site. A reference (control) TEWL measurement will
be taken from intact skin at an anatomically matched site on the patient. A high TEWL/
defective closure is defined as a TEWL value =2 times the value of the patient's control
measurement. Patients who meet this criterion will be randomized to one of four groups:
EpiCeram treatment, Ceramiseal treatment, Vaseline treatment or no treatment. Patients
randomized to a treatment group will be supplied with study product and will be instructed to
apply twice daily to the closed wound site for the remaining weeks of the study. All High
TEWL patients will be asked to return for Study Visits 3-6. Distribution of study product as
applicable. For this study, a low TEWL/ adequate closure is defined as a value less than 2
times the value of the patient's control measurement. Patients who meet this criterion will
not be randomized into a treatment group, but will continue to receive standard of care per
their physician and will be asked to return for study visits 3, 4, and 6. During these last
visits the following activities will occur: TEWL measurements, digital imaging, sequential
tape stripping to measure ceramide levels in the skin (up to 20 tape strips obtained). TEWL
measurements will be obtained prior to tape stripping. The tape strips be completed after the
TEWL measurements are obtained, wound site evaluation, various labs, medications review,
distribution of study product (High TEWL only) and review of compliance and a quality of life
survey is completed by the subject(visit 6 only). There may be some discomfort with the
tissue biopsy procedure depending on the amount of sensation the subject has at the site of
the wound and will be numbed by applying local anesthesia as appropriate to area being
biopsied. The amount of pain that occurs with wound biopsies will vary from person to person,
but all efforts will be made to minimize pain and is within the boundaries of the existing
wound to avoid giving the patient a separate new wound. Bleeding is a possible complication,
but the risk is low for the small biopsies and is reduced by using local anesthetics with
epinephrine, and silver nitrate sticks are available in each patient room to cauterize biopsy
sites as needed. Infection is also a potential risk; however, wound tissue biopsies are
routinely performed as the standard of care in the CWC to diagnose wound infection. The
biopsy site will be appropriately monitored for infection by the physician managing the wound
during routine wound clinic visits.Possible risks for the use of the ceramide emulsion
EpiCeram® are a temporary tingling sensation (10-15 minutes) and an extremely low risk of an
allergic reaction. If this occurs the application of the cream will be stopped immediately.
Possible risks for the use of Vaseline Petroleum and Ceramiseal™ are very low should be
stopped if an allergic reaction occurs.There can be some minor redness and discomfort at the
site of the tape stripping. The skin remains intact, i.e. the epidermis is not breached after
the tape stripping procedure making this less than minimal risk. TEWL measurements are
noninvasive and propose less than minimal risk.

Inclusion Criteria:

- Age ≥ 18

- Willing to comply with protocol instructions, including all biopsies, study visits and
study activities.

- One of the following:

1. Chronic wound of multiple etiologies and open for at least 30 days, including:

1. Diabetic foot ulcers, Wagner grade 1-3

2. Pressure ulcers, stage 2-3

3. Venous leg ulcers, confirmed by venous duplex

4. Burn wounds open

5. Clinical contraindication to biopsy in the opinion of the wound care
physician

2. Wounds not appropriate for biopsy due to either:

1. Almost healed at the time of enrollment (per physician)

2. Healed within 10 days prior to enrollment visit

3. Other etiology, deemed appropriate for biopsy

- Adequate arterial blood flow as evidenced by at least one of the following:

1. Transcutaneous oxygen measurement (TcOM) > 30 mmHg

2. Ankle-brachial index ≥0.7

3. Toe pressure > 30 mmHg

Exclusion Criteria:

- Individuals who are deemed unable to understand the procedures, risks and benefits of
the study, (i.e. unable to provide informed consent)

- Diabetics with Hemoglobin A1c > 10%

- Subjects with marked immunodeficiency (HIV/AIDS, organ transplant patients and cancer
patients and patients with autoimmune disease on immunosuppressive medications).

- Wounds closed or to be closed by flap or graft coverage - including stage 4 pressure
ulcers and Wagner grade 4 or 5 diabetic foot ulcers

- Prisoners

- Patients with allergies to petrolatum

- Patients who are currently enrolled in another research study which includes
investigational treatment and/or medication