Efficacy of LL-37 Cream on Bacteria Colonization, Inflammation Response and Healing Rate of Diabetic Foot Ulcers

Study Overview
=================
Brief Summary
-----------------
Diabetic foot ulcer (DFU) is a common complication of diabetes with global prevalence of 6.3%. Treatment of diabetic foot ulcer (DFU) is challenging with disappointing outcome. Wound debridement, infection control, pressure relief and revascularization are main pillars of DFU management. Various substances and modalities are being investigated for their potential effects in treating DFU, one of which is LL-37. In this randomized, controlled trial, 40 patients with uncomplicated DFU will be enrolled. Patients are randomly assigned to undergo twice a week treatment with 0.5 mg/mL LL-37 cream (treatment group) or placebo cream (control group) for 4 weeks in addition to standard wound care. The primary outcomes are the healing rate measured by wound area and granulation index and changes in patterns of aerobic bacteria colonization during the 4-week study duration and changes in concentrations of IL-α and TNF-α from fluid collected from DFU on the end of the second and third week of study compared to baseline.

Official Title
-----------------
The Efficacy of LL-37 Cream on Aerobic Bacteria Colonization Pattern, Inflammation Response: Interleukin 1α (IL-1α) and Tumor Necrosis Factor α (TNF-α), and Healing Rate of Diabetic Foot Ulcers

Conditions
-----------------
Diabetic Foot Ulcer

Intervention / Treatment
-----------------
* Drug: LL37
* Procedure: Standard Wound Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with DFU Ankle brachial index (ABI) 0.9 - 1.3 Wound area 5 - 20 cm^2 Wound depth until subcutaneous tissue Without systemic infection, osteomyelitis, septic arthritis, or fasciitis Subjects are willing to participate by signing consent Exclusion Criteria: Gangrene On treatment with systemic corticosteroids within 7 days before the start of study On treatment with systemic antibiotics within 2 days before the start of study Patients with end stage renal disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>0.5 mg/mL LL-37 cream, administered twice a week for 4 weeks | Drug: LL37<br>* cream<br>Procedure: Standard Wound Care<br>* Standard wound debridement<br>|
| Placebo Comparator: Placebo<br>Placebo cream, administered twice a week for 4 weeks | Procedure: Standard Wound Care<br>* Standard wound debridement<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Healing Rate at 1 Week | Measured by difference of granulation index by ImageJ | Changes from baseline of granulation index at 1 week | 
| Changes of Healing Rate at 2 Week | Measured by difference of granulation index by ImageJ | Changes from baseline of granulation index at 2 weeks | 
| Changes of Healing Rate at 3 Week | Measured by difference of granulation index by ImageJ | Changes from baseline of granulation index at 3 weeks | 
| Changes of Healing Rate at 4 Week | Measured by difference of granulation index by ImageJ | Changes from baseline of granulation index at 4 weeks | 
| Changes of Aerobic Bacteria Count and Type of Bacteria Species at 1 Week | Measured by the species of bacteria grown on culture and the quantities of their colonies in CFU/swab | Changes from baseline of the species of bacteria grown on culture and the quantities of their colonies in CFU/swab at 1 week | 
| Changes of Aerobic Bacteria Count and Type of Bacteria Species at 2 Week | Measured by the species of bacteria grown on culture and the quantities of their colonies in CFU/swab | Changes from baseline of the species of bacteria grown on culture and the quantities of their colonies in CFU/swab at 2 week | 
| Changes of Aerobic Bacteria Count and Type of Bacteria Species at 3 Week | Measured by the species of bacteria grown on culture and the quantities of their colonies in CFU/swab | Changes from baseline of the species of bacteria grown on culture and the quantities of their colonies in CFU/swab at 3 week | 
| Changes of Aerobic Bacteria Count and Type of Bacteria Species at 4 Week | Measured by the species of bacteria grown on culture and the quantities of their colonies in CFU/swab | Changes from baseline of the species of bacteria grown on culture and the quantities of their colonies in CFU/swab at 4 week | 
| Changes of Inflammation Marker at 2 Week | Measured by the concentrations of IL-α and TNF-α by ELISA | Changes from baseline at the end of second week | 
| Changes of Inflammation Marker at 3 Week | Measured by the concentrations of IL-α and TNF-α by ELISA | Changes from baseline at the end of third week |