Treatment of Chronic Wound Biofilms

Study Overview
=================
Brief Summary
-----------------
Chronic wounds cause significant morbidity and cost our healthcare system millions of dollars each year.Their healing is slowed by biofilms, communities of bacteria surrounded by a protective layer that stops the immune system and antibiotics from getting close enough to kill them. The investigators will develop a new strategy to destroy biofilms using a protein made from bacteria that live on our skin.The Staphylococcus epidermidis Esp protein will be used to destroy Staphylococcus aureus biofilms, the most common bacterium in chronic wounds. The investigators hypothesize that the use of the Esp protein will breakdown S. aureus biofilms, decrease bacterial colonization of chronic wounds and improve healing times.

Detailed Description
-----------------
Chronic wounds lead to significant patient morbidity and mortality, and its treatment is associated with a global economic burden of $13-$15 billion annually. In Canada, the average cost of three months of community care for a chronic wound is $ 27,600.00. One of the major complications associated with chronic wounds is colonization with a Staphylococcus aureus (S. aureus) biofilm. These bacterial biofilms delay re-epithelialization and prevent wound healing. Standard treatment of chronic wound biofilms includes aggressive debridement as well as the addition of anti-biofilm agents such as antimicrobials. Since antimicrobial resistance is becoming a serious problem, finding alternatives is essential. Staphylococcus epidermidis (S. epidermidis) JK16 cells, their culture supernatants and a serine protease (Esp) in the culture supernatants have been shown to inhibit the formation of and destroy preexisting S. aureus biofilms. The investigators hypothesize that the use of S. epidermidis JK16, culture supernatants or purified Esp protein in the standard wound care protocol will breakdown S. aureus biofilms, decrease bacterial colonization of chronic wounds and improve healing times. The investigators will employ a two-way cross over study where participants will receive standard wound care or S. epidermidis JK16 Esp supplemented treatment for the first 6 weeks followed by cross over for a further 6 weeks. These patients will be recruited from the Wound Healing Clinic at Vancouver General Hospital. Standard wound care will be provided in accordance with established protocols based on Best Clinical Practice Guidelines for Venous Leg Ulcers from the Canadian Association of Wound Care. For the S. epidermidis JK16 Esp supplemented treatment arm, the investigators will produce purified Esp and impregnate wound dressings with this protein. After 6 weeks, participants will be crossed over to the corresponding treatment arm. Our primary outcome measure will be healing rate as calculated for each 6 week standard or experimental treatment periods. The investigators will employ standardized photography and wound image analysis software to calculate the healing rate. Other outcome measures will include visual detection and qualitative assessment of biofilms as determined by trained nurses and/or physicians. Finally, bacterial type and quantity will be determined by wound biopsy. Outcome measures for standard treatment arms will be compared with results from S. epidermidis JK16 Esp supplemented treatment arms. Objectives of this pilot study include: To assess the feasibility of conducting a more definitive trial to examine the efficacy of S. epidermidis Esp protein from strain JK16 in healing chronic wounds To perform a pilot study using a cross-over design with the purified S. epidermidis Esp protein from strain JK16 in comparison to standard therapy To demonstrate that the intervention is acceptable to participants To demonstrate the safety of the intervention To explore the biologic activity of S. epidermidis Esp protein from strain JK16 on wound biofilms and healing times

Official Title
-----------------
Treatment of Chronic Wound Staphylococcus Aureus Biofilms With Staphylococcus Epidermidis Esp Protein to Promote Healing

Conditions
-----------------
Chronic Wound, Venous Insufficiency, Biofilms

Intervention / Treatment
-----------------
* Biological: Esp protein
* Other: Standard wound care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a leg ulcer with the ankle brachial pressure index (ABPI) equal or greater than 0.6; Have a wound that is 15 cm or less in diameter; Are 19 years or older; Have no known contraindication to the treatment products Exclusion Criteria: Have a leg ulcer caused by pressure, diabetes, ischemia, inflammatory disorder, hematologic disorder or malignancy Have applied an antiseptic to the wound in the one week prior to recruitment Have received systemic or topical antibiotic therapy within 48 hours prior to recruitment Are being treated with systemic steroids (prednisone)

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esp-supplemented standard wound care<br>500 pmol Esp protein will be added to the standard wound care protocol. | Biological: Esp protein<br> <br> |
| Active Comparator: Standard wound care<br>The standard treatment protocol established at the Vancouver Wound Healing Clinic is based on the Best Clinical Practice Guidelines for Venous Leg Ulcers from the Canadian Association of Wound Care. | Other: Standard wound care<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of wound healing | The rate of wound healing (% change in wound surface area) over each 6-week treatment period. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A qualitative assessment of the healing process. | A physician or nurse will record a visual assessment of the chronic wound in order to obtain a qualitative wound score. | 1 week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic wound, treatment, biofilms, venous insufficiency, Esp