Preventing Diabetic Foot Ulcers Through Cleaner Feet

Preventing Diabetic Foot Ulcers Through Manipulating the Skin Microbiota

Foot complications are among the most serious and costly complications of diabetes. People with diabetes have a 10-fold increased risk for a leg or foot amputation compared to those that do not have diabetes. Amputation of all or part of foot is usually preceded by a foot ulcer, which became infected. This is a clinical trial to test the effectiveness of a topical antiseptic, chlorhexidine, for daily foot cleaning on the occurrence of diabetic foot ulcers in Veterans at high risk of a diabetic foot ulcer.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Drug: Chlorhexidine; Drug: Placebo

Detailed Description

Population: Up to 200 Veterans at high risk of a diabetic foot ulcer

Site: VA Maryland Health Care System (VAMHCS)

Study Duration: Approximately 5 years

Study Design: Randomized double-blind clinical trial comparing a) a daily foot care regimen with cloths containing 2% chlorhexidine to b) a daily foot care regimen with cloths not containing 2% chlorhexidine

Objectives:

Primary: To determine if chlorhexidine reduces the occurrence of foot complications including chronic foot ulcer, foot infection or foot amputation.

Secondary: To determine if chlorhexidine increases antibiotic resistance among bacterial pathogens on feet.

Exploratory: To describe changes in the microbiota of the feet with chlorhexidine and foot complications

Treatment Regimens: 2% Chlorhexidine Gluconate Cloths versus Bath Cloths

Route of Administration: Topical application on the feet

Dose and Interval: 1 cloth daily

Duration of Participant's Participation: Up to 13 months

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults >=18 years
• Clinical diagnosis of diabetes
• At high risk for a new diabetic foot ulcer due to: 1)Past history of diabetic foot ulcer or 2)Past history of major foot surgery including partial foot amputation or 3)Past history of major foot infection or 4)Neuropathy and onychomycosis and hemoglobin A1C >8% or 5)Neuropathy and peripheral vascular disease or 6)Dialysis or 7)Past history of Charcot foot or 8)Past history of peripheral vascular surgery or angiography with stent
• Two feet (can have amputation of part of the foot)
• At least one foot without a foot ulcer
• Permanent mailing address suitable for provision of specimen collection materials and telephone suitable for monthly follow-up
• Able to give written informed consent

Exclusion Criteria:

• Amputation of the foot planned to treat current foot ulcer or wound
• Current foot infection
• Use of topical chlorhexidine on feet 7 days prior to randomization
• History of an allergic reaction to chlorhexidine
• Unable to use wipes for foot care
• Inability to walk
• Life expectancy less than 12 months
• Plans to move out of the area in the next 13 months
• Requires equivalent of institutional care (e.g. nursing home)
• Any other criteria which, in the investigator's opinion, would compromise the safety of the study, the ability of a subject to participate, or the results of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chlorhexidine; Participants randomized to the intervention will wash their feet using 2% CHLORHEXIDINE GLUCONATE CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.	Drug: Chlorhexidine; Participants randomized to the intervention will wash their feet using 2% CHLORHEXIDINE GLUCONATE CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.
Placebo Comparator: Placebo; Participants randomized to the placebo will wash their feet using COMFORT BATH CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.	Drug: Placebo; Participants randomized to the placebo will wash their feet using COMFORT BATH CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to New Foot Complication Among All Randomized Participants	Time in days to new foot complication (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to new foot complication; the results we are reporting are number of participants who developed a new foot complication in the 12 months post randomization). A new foot complication is defined as either 1) a new chronic (present 28 days from initial diagnosis) foot ulcer or wound or 2) a moderate or severe foot infection (as defined by IDSA Diabetic Foot Infection Severity classification: Table 2) not from an existing ulcer or 3) a foot amputation for a new ulcer.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Susceptibility to Chlorhexidine Among Bacterial Pathogens on the Feet	Susceptibility to chlorhexidine among bacterial pathogens on the feet. Chlorhexidine minimum inhibitory concentration (MIC) values were normalized across pathogens by subtracting the median MIC value (MIC50) from the literature for each pathogen from the observed MIC value on a log2() scale. The results we are reporting are the mean normalized MIC values and the Wilcoxon Rank Sum test comparing the difference in distribution of normalized MIC values. Effect size is expressed in means as this is more sensitive to group differences than the median. The possible range for the normalized observed MIC values on a log2() scale is from -8 to 8 with a higher value indicating that the pathogens collected were more resistant to chlorhexidine as compared to the median MIC values reported in the literature.	4 weeks after stopping the intervention (approximately 13 months after randomization)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to New Foot Complication Among Participants With a Healed Foot Complication at Randomization.	Time in days to new foot complication (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to new foot complication; the results we are reporting are number of participants who developed a new foot complication in the 12 months post randomization). A new foot complication is defined as either 1) a new chronic (present 28 days from initial diagnosis) foot ulcer or wound or 2) a moderate or severe foot infection (as defined by IDSA Diabetic Foot Infection Severity classification: Table 2) not from an existing ulcer or 3) a foot amputation for a new ulcer.	12 months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Mary-Claire Roghmann, MD, Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): January 6, 2023

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: prevention; clinical trial; topical chlorhexidine
• 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; Anti-Infective Agents, Local; Anti-Infective Agents; Disinfectants; Chlorhexidine
• Other Study ID Numbers: INFB-015-17F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Final data sets underlying all publications resulting from the proposed research will be shared outside VA. A limited dataset will be created and shared pursuant to a Data Use Agreement. Final data sets will be maintained locally until enterprise-level resources become available. Upon request, we will provide an electronic limited dataset to others in the scientific community with the implementation of appropriate data use agreements.
• IPD Sharing Time Frame: The study protocol and statistical analysis plan are available now on the CT.gov page for this study. Final datasets underlying all publications will be made available upon publication of each paper.
• IPD Sharing Access Criteria: Implementation of appropriate data use agreements. Email the study PI, Dr. Mary-Claire Roghmann (mroghmann@som.umaryland.edu), to start the process.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No