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

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Drug: LL37; Procedure: Standard Wound Care

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta, DKI Jakarta, Indonesia, 13230
      • RS Persahabatan
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • RSUPN Dr. Cipto Mangunkusumo
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10410
      • RS Pusat Angkatan Darat Gatot Soebroto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Fakultas Kedokteran Universitas Indonesia
• Investigators: Principal Investigator: Eliza Miranda, MD, Fakultas Kedokteran Universitas Indonesia

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 22, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer; Inflammation
• Other Study ID Numbers: 19-09-1128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No