Preventing Diabetic Foot Ulcers Through Manipulating the Skin Microbiota
Phase: PHASE2
Conditions: Diabetic Foot Ulcer
Sponsor: VA Office of Research and Development

 
PROTOCOL NAME 
Grant Title: Preventing Diabetic Foot Ulcers through Manipulating the Skin Microbiota 
Short title: Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
CICERO protocol number: HP-79894 
Modification #: 22 
Version #: 15.0 
PROTOCOL VERSION DATE: 1/25/2023 
 
 
Commonly Used Abbreviations 
S. aureus
Staphylococcus aureus
VAMHCS 
Veterans Affairs Maryland Health Care System
PAVE
Prevention of Amputation in Veterans Everywhere
R&D
Research and Development
VHA
Veterans Health Administration
UMB 
University of Maryland Baltimore 
IRB
Institutional Review Board
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
2
GENERAL INFORMATION 
 
 
Name and address of the study monitor and person authorized to sign the protocol and 
amendments:  
 
Mary-Claire Roghmann, MD, MS 
Infectious Disease Staff Physician and Research Health Scientist 
Head, Epidemiology Section 
Medical Care Clinical Center 
VA Maryland Health Care System 
 
Professor of Epidemiology and Public Health and Medicine 
University of Maryland School of Medicine 
10 S. Pine St., MSTF 3-36 
Baltimore, MD 21201 
Phone   
 
(410) 706-0062 
Fax  
 
 
(410) 706-0098 
E-mails 
 
mroghmann@som.umaryland.edu 
 
 
 
Mary-Claire.Roghmann@va.gov 
 
Name and addresses of the laboratories, study sites and/or other institutions involved in the 
study: 
Laboratories-
Participant Recruitment Sites-
Baltimore VA Medical Center 
Microbiology Research Lab, 3C-112 
10 North Greene Street 
Baltimore, MD 21201 
 
Baltimore VA Medical Center 
Outpatient Clinics 
10 North Greene Street 
Baltimore, MD 21201 
Microbiology Research Lab 
Department of Pathology 
Allied Health Building, Room 401 and 450 
100 Penn Street 
Baltimore, MD 21201 
 
Loch Raven VA Community based Outpatient 
Clinics 
3900 Loch Raven Boulevard 
Baltimore, MD 21218 
 
 
 
Perry Point VA Medical Center 
Outpatient Clinics 
Perry Point, MD 21902 
 
Study form storage- 
University of Maryland School of Medicine 
MSTF 360 
10 South Pine Street 
Baltimore, MD 21201 
Clinical visits- 
VA Medical Healthcare Centers 
 
 
 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
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Revision History-Modifications made within the protocol and/or consent 
 
Protocol Version 
Date 
Amendments 
V 15.0 
01/25/2023 
1. Modified study variables in Appendix to 
accurately reflect what was collected during the 
study. 
2. Removed specific antibiotics we are testing
V 14.0 
07/06/2022 
1. Changed the time in the study to be 15 months and 
not 13 months. 
2. Added organisms we are culturing swabs for
V 13.0 
8/12/2020 
1. The V7 visit was changed to after 2 weeks instead 
of 2-6 weeks 
2. In the ICF, it was added that photos will only be 
used to assess foot health.
V 12.0 
6/30/2020 
1. Combined the ICF and HIPAA in one document 
2. Added the ability to consent remotely 
3. Editorial changes to be consistent with other 
documents 
4. Added that one bag per participant kit will be kept 
to make sure the correct wipe was distributed to 
the participant
V 11.0 
5/18/2020 
1. Revised sites for clinical visits to be anywhere in 
the VAMHCS 
2. Added ability to pay participants with a gift card 
3. Added participants that are having remote visits 
will self-swab their feet and take photos of their 
feet. 
4. Added instructions on how to take foot swabs. 
5. Added instructions on how to take foot photos 
6. Editorial changes to be consistent with other 
documents
V10.0 
03/11/2020 
1. Made edits to the protocol to be consistent with the 
informed consent document 
2. Edited to remove nasal swabs if participant 
exhibits respiratory symptoms 
3. Edited to make changes to study visits related to 
COVID-19
V9.0
02/06/2020
1. Modified when visit 7 could occur
V8.0 
9/26/2019 
2. Added language related to transfer of data to and 
from CRISP
V7.0 
8/27/2019 
1. Modified the eligibility criteria 
2. Added language to include a final visit for 
participants who were randomized and were 
withdrawn from the study. 
3. Updated the definition for study primary/secondary 
endpoint

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
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4. We added an informational flyer for VA providers 
as a way of providers to refer patients that may be 
eligible for the study. 
5. We updated our flyer and introductory letter for 
veterans with the new eligibility criteria
V6.0 
4/29/2019 
1. Modified the eligibility criteria 
2. Added language to include the option of receiving 
weekly medication reminder texts through the 
Annie App instead of from a cell phone. 
3. We added the ability to follow-up with participants 
if they are eligible, interested in the study, but want 
to review the protocol at home first
V5.0 
 
1. Modified the eligibility criteria 
2. We changed the outcome definition to indicate that 
we are aiming to prevent new foot complications. 
3. Modified the study variables that are being 
collected.
V4.0 
12/19/2018 
1. Added language to withdraw participant if they 
reach the end-point. 
2. Modified the eligibility criteria 
3. Adding a 7th skin site on the foot and an 8th swab 
for chlorhexidine testing 
4. Made changes to the initial interaction with 
potential participant. 
5. Modified the study variables that are being 
collected.
V3.0 
9/21/2018 
1. Removed monthly sampling of feet and mailing of 
specimens 
2. Added photography of feet 
3. Added language to be clearer what was being done 
at each visit 
4. Added language to include monthly calls about 
health and weekly texts/calls as medication 
reminders 
5. Added to participant responsibilities: respond to 
contact from staff 
6. Increased compensation to $50 per visit and 
removed language about compensation for 
monthly self-swabs.  Total compensation = $350 
7. Added language about CRISP 
8. Added clinicaltrials.gov # and type of clinical trial 
9. Modified the eligibility criteria 
10. Added language about when the eligibility criteria 
needed to be signed 
11. Added the information about an introductory letter 
and opt-out procedures 
12. Study cloths will be repackaged with seven cloths 
per package instead of one

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
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13. Added more detail about signs of intolerance 
14. Added the ability to use VINCI 
15. Modified the Data Collection, Handling and 
Storage section to reflect the collection of full 
SSNs, not just the last 4 digits. 
16. Modified the analysis plan and sample size 
calculations 
17. Increased the sample size in order to compensate 
for potential withdrawal of study participants. 
18. Modified language related to repackaging and 
storage of study product to indicate that study staff 
will be repackaging wipes and study product will 
be stored outside of the VA investigational 
pharmacy. 
V2.0 
5/17/2018 
No changes to the protocol. The following was modified 
within the IRB protocol and HIPAA 
1. Additional questions were addressed within 
CICERO  
2. The IRB was updated with the ClinicalTrials.gov 
number.   
3. A version date was added to the HIPAA document
V1.0
5/14/2018
N/A – Original Protocol

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
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Table of Contents 
PROTOCOL SUMMARY .......................................................................................................................................... 7 
LAY SUMMARY ........................................................................................................................................................ 7 
1 
BACKGROUND INFORMATION AND RATIONALE .............................................................................. 8 
1.1 
BACKGROUND AND RATIONALE ................................................................................................................................. 8 
1.2 
RISK/BENEFITS ........................................................................................................................................................... 8 
1.3 
STUDY CONDUCT ........................................................................................................................................................ 9 
2 
STUDY OBJECTIVES .................................................................................................................................... 9 
3 
STUDY DESIGN ............................................................................................................................................ 10 
3.1 
PRIMARY STUDY ENDPOINTS/SECONDARY ENDPOINTS ............................................................................................ 10 
4 
STUDY DESIGN/TYPE ................................................................................................................................. 10 
4.1 
DURATION ................................................................................................................................................................ 10 
5 
SELECTION AND WITHDRAWAL OF PARTICIPANTS ...................................................................... 10 
5.1 
SELECTION OF STUDY POPULATION .......................................................................................................................... 10 
5.2 
INCLUSION CRITERIA ................................................................................................................................................ 10 
5.3 
EXCLUSION CRITERIA ............................................................................................................................................... 11 
5.4 
PARTICIPANT WITHDRAWAL..................................................................................................................................... 11 
6 
INFORMED CONSENT PROCESS ............................................................................................................ 11 
6.1 
RECRUITMENT .......................................................................................................................................................... 11 
6.1.1 
Distribution of IRB approved informational flyer .......................................................................................... 12 
6.1.2 
Mailing of an Introductory letter and an opt out card.................................................................................... 12 
6.2 
INFORMED CONSENT ................................................................................................................................................. 13 
7 
STUDY INTERVENTION ............................................................................................................................ 13 
7.1 
STUDY PRODUCT DESCRIPTION ................................................................................................................................ 13 
7.1.1 
Acquisition ...................................................................................................................................................... 13 
7.1.2 
Formulation, Packaging, and Labeling .......................................................................................................... 14 
7.1.3 
Product Storage and Stability ......................................................................................................................... 14 
7.2 
DOSAGE, PREPARATION AND ADMINISTRATION OF STUDY INTERVENTION .............................................................. 14 
7.3 
MODIFICATION OF STUDY INTERVENTION ................................................................................................................ 14 
7.4 
ACCOUNTABILITY PROCEDURES FOR THE STUDY INTERVENTION ............................................................................. 14 
7.5 
ASSESSMENT OF PARTICIPANT COMPLIANCE WITH STUDY INTERVENTION .............................................................. 14 
8 
STUDY PROCEDURES/EVALUATIONS .................................................................................................. 15 
8.1 
STUDY VISITS ........................................................................................................................................................... 16 
8.2 
LABORATORY EVALUATIONS.................................................................................................................................... 17 
8.3 
CLINICAL EVALUATIONS .......................................................................................................................................... 17 
9 
UNANTICIPATED PROBLEMS AND SERIOUS ADVERSE EVENTS ................................................ 17 
10 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................................................ 17 
11 
STATISTICAL PLAN ................................................................................................................................... 17 
11.1 ANALYSIS PLAN ........................................................................................................................................................ 17 
11.1 SAMPLE SIZE CALCULATION ..................................................................................................................................... 18 
12 
ETHICAL CONSIDERATIONS................................................................................................................... 18 
13 
DATA COLLECTION, HANDLING AND STORAGE ............................................................................. 18 
14 
VA INFORMATICS AND COMPUTING INFRASTRUCTURE (VINCI) ............................................. 19 
15 
CHESAPEAKE REGIONAL INFORMATION SYSTEM FOR OUR PATIENTS (CRISP) ................. 22 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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Protocol Summary 
 
Population: Up to 200 veterans at risk for diabetic foot ulcers  
 
Site: VA Maryland Health Care System (VAMHCS) 
 
Study Duration: Approximately 5 years 
 
Clinical Trial: Phase IIb 
 
Clinicaltrials.gov #: NCT03503370 
 
IND exempt 
 
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 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: SAGE 2% Chlorhexidine Gluconate Cloths versus SAGE Comfort Bath 
Cloths 
 
Route of Administration: Topical application on the feet 
 
Dose and Interval: 1 cloth daily 
 
Duration of Participant’s Participation: Up to 15 months 
Lay Summary 
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 reducing new foot complications including chronic foot 
ulcer or wound, foot infection, or foot amputation in Veterans at high risk for a foot ulcer. 
 
Keywords: Foot ulcer, diabetes, topical chlorhexidine, prevention, clinical trial 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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1 
Background Information and Rationale  
1.1 
Background and Rationale  
Between 10 and 25% of people with diabetes will develop a foot ulcer during their 
lifetime. Foot ulcers are a leading cause of hospitalization in people with diabetes and the 
primary cause of non-traumatic amputation. About 40% of people with diabetes with a recently 
resolved foot ulcer will have a recurrence within one year despite current prevention efforts. 
Thus the development of new interventions to decrease the risk of foot ulcers in high risk people 
is urgently needed. The prevalence of diabetes in the Veterans Health Administration’s patient 
population is about 24% making this a priority clinical issue for veterans’ care. 
 
A foot ulcer typically begins with minor trauma to the foot in a patient with diabetic 
neuropathy. The minor skin trauma fails to heal resulting in a skin ulcer. The ulcer leads to 
infection, particularly due to Staphylococcus aureus, and often to gangrene resulting in an 
amputation. The role of the skin microbiota in the development of foot ulcers is unknown. 
Multiple skin disorders and infections are hypothesized to result from imbalance in the 
microbiota and the host inflammatory and immune responses. Impaired wound healing is 
hypothesized to result in part from dysregulated inflammation and microbial colonization 
suggesting a possible mechanism by which the skin microbiota could promote faulty wound 
healing after a minor trauma leading to a foot ulcer. 
 
Prior work has shown that the feet of diabetic veterans have an increased S. aureus load 
compared with non-diabetic veterans. Our preliminary data suggest that there is an increased S. 
aureus and total bacterial load on the feet of diabetic veterans at high risk for future foot ulcer 
compared to diabetic veterans at low risk of a future foot ulcer. We also found a higher relative 
abundance of staphylococci in the skin microbiota on the heels of people with diabetes at high 
risk for foot ulcers compared to those at low risk. Thus our data suggest that there are absolute 
differences in bacterial load and perhaps relative differences in abundance of bacterial taxa on 
the feet which could be part of the causal pathway for developing a foot ulcer. If so, altering the 
skin microbiota of the feet could reduce the risk of foot ulcers. 
 
Chlorhexidine is a potential intervention to decrease the risk of diabetic foot ulcer through 
reducing the bacterial and fungal load including skin pathogens such as S. aureus. It is a broad-
spectrum antiseptic agent with an excellent safety profile. It prevents healthcare associated 
infections, such as surgical site infection, after iatrogenic skin breakdown through reducing the 
microbial load on the skin which has similarities to the pathogenesis of diabetic foot ulcers. To 
explore the effect of chlorhexidine on the skin microbiota of the foot, we had Veterans with 
diabetes at high risk for foot ulcer use chlorhexidine on their feet. We found an absolute decrease 
in S. aureus and overall bacterial load and a decrease in the relative abundance of staphylococci 
among the foot microbiota. Thus we propose the following study to test the effect of 
chlorhexidine reduces new diabetic foot ulcers.  
 
1.2 
Risk/Benefits 
The risks of the proposed study are minimal. There are possible risks and discomforts 
from this study for participants. 
 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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SAGE® 2% CHLORHEXIDINE GLUCONATE* CLOTH is an FDA- approved 
formulation and application for topical 2% chlorhexidine, an antiseptic solution which is 
available without a prescription. It is widely used for pre-operative skin cleansing and extremely 
well tolerated. Mild skin irritation can occur; this stops after chlorhexidine is stopped. A 
systemic allergic reaction including low blood pressure can occur; this is very rare. 
 
SAGE® COMFORT BATH CLOTHS is a cloth soaked in mild, rinse-free cleansers and 
skin-protecting moisturizers like aloe and vitamin E, which is available without a prescription. It 
is widely used for bathing hospitalized patients and extremely well tolerated. An allergic reaction 
could occur; this is very rare. 
 
The sampling methods for the anterior nares and skin sites is physically non-invasive, but 
there could be some discomfort during the procedure. The potential discomfort from obtaining 
the specimens does not place any participant at physical risk. A trained research coordinator will 
use very gentle pressure while obtaining the specimen to minimize these risks. 
 
There is a risk that health information could be in accidentally disclosed to others outside 
the study. There is a potential for breach of privacy.  Privacy and Confidentiality will be 
protected to the extent permitted by law. 
 
There may be adverse events that are not yet known.  
 
There is no alternative treatment or procedure to participating in this study, but 
individuals have the right to decline participation in this research without any prejudice to their 
care or benefits. 
 
There are potential direct benefits to study participants. Participants will receive 
education on foot self-care. Participants receiving either regimen will have cleaner feet. This 
study will provide knowledge to determine whether topical chlorhexidine might be used to 
prevent diabetic foot ulcers and their complications. 
1.3 
Study Conduct 
This study will be conducted in compliance with the protocol approved by the UMB 
Institutional Review Board (hereafter referred to as IRB) and VAMHCS R&D Committee and 
according to Good Clinical Practice standards and the VHA Handbook 1200.05 Requirements 
for the Protection of Human Subjects in Research.  No deviation from the protocol will be 
knowingly implemented without the prior review and approval of the IRB except where it may 
be necessary to eliminate an immediate hazard to a research participant.  In such case, the 
deviation will be reported to the IRB as soon as possible. 
2 
Study Objectives 
 
Primary: To determine if chlorhexidine reduces new 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. 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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3 
Study Design 
3.1 
Primary Study Endpoints/Secondary Endpoints 
Foot complications. We will assess participants for new foot complications to include: new 
chronic foot ulcers or foot infections or foot amputations on a monthly basis. Our primary 
outcome is time from randomization until 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 IDSA 
Diabetic Foot Infection Severity classification: Table 21) not from an existing ulcer or 3) a foot 
amputation for a new ulcer.  
 
Susceptibility to chlorhexidine and other antibiotics among bacterial pathogens. Participants will 
have cultures performed with a nylon flocked swab at enrollment and at 13 months 
approximately 4 weeks after stopping the intervention. 
4 
Study Design/Type 
This is a multi-center, randomized, double blind (participant, outcome assessor), parallel group 
clinical trial comparing daily foot care with cloths containing 2% chlorhexidine compared to 
daily foot care with cloths not containing chlorhexidine. 
4.1 
Duration 
Study participants will have study visits over a period of up to 15 months. 
5 
Selection and Withdrawal of Participants 
5.1 
Selection of Study population 
All study participants will be recruited from the outpatient population in the VA Maryland 
Health Care System. Some eligibility criteria cannot be assessed on the date of consent.  
Therefore, the eligibility checklist can be signed any time before the date of randomization. 
5.2 
Inclusion Criteria 
 Adults >= 18 years 
 Clinical diagnosis of diabetes 
 At risk for a new diabetic foot ulcer due to:  
1) Past history of a diabetic foot ulcer or  
2) Past history of major foot surgery including partial foot amputation (e.g. toe) 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 amputations of part of the foot) 
 At least one foot without a foot ulcer 
 
1 Benjamin A. Lipsky, Anthony R. Berendt, Paul B. Cornia, James C. Pile, Edgar J. G. Peters, David G. Armstrong, 
H. Gunner Deery, John M. Embil, Warren S. Joseph, Adolf W. Karchmer, Michael S. Pinzur, Eric Senneville, 2012 
Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic 
Foot Infections, Clinical Infectious Diseases, Volume 54, Issue 12, 15 June 2012, Pages e132–
e173, https://doi.org/10.1093/cid/cis346 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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 Permanent mailing address suitable for provision of specimen collection materials and 
telephone suitable for up to weekly follow-up 
 Able to give written informed consent 
5.3 
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.  
5.4 
Participant Withdrawal 
Study participants will be withdrawn from the study if found to have been initially 
ineligible or intolerant of the study procedures.  Study participants who have missed two 
consecutive study visits will no longer be contacted regarding additional study visits and will not 
receive additional study intervention products (wipes and swabs).  Study participants whose 
study visits are re-scheduled as part of the safety concerns related to COVID-19 will still be 
contacted regarding the study and will still receive study supplies if they indicate they would like 
to still be in the study. However, study participants who have missed two consecutive visits or 
have been randomized to the study intervention and then withdrawn from the study can contact 
study staff and return for a visit #7 (outlined below) at any point prior to 1-year post 
randomization. This visit #7 should be performed at least 2 weeks after the participant stops 
taking study medication. Study staff will continue to perform medical record review for foot 
ulcers, infection or amputation and record clinical management of ulcers, infection or amputation 
for withdrawn participants unless the participant specifically requests otherwise.  
 
Study participants will also be withdrawn if they reach the primary study endpoint before 13-
months.  
6 
Informed Consent Process 
6.1 
Recruitment 
We are requesting a partial HIPAA waiver for recruitment to allow study staff to review 
administrative data from the VAMCHS Podiatry Service and then the medical record of potential 
participants to determine initial eligibility. Study staff will review and document the 
administrative data and then medical records of potential participants to determine if they meet 
eligibility criteria.  Accessing this information from administrative data and the participant’s 
medical record reduces the burden on the participant with regard to time and research 
procedures, increases the feasibility of the study, and confers no more than minimal, additional 
risk. 
 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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All study participants will be recruited from the VA Maryland Health Care System. They 
will be identified by administrative codes used for Prevention of Amputation in Veterans 
Everywhere (PAVE) initiative or by using the VA Informatics and Computing Infrastructure 
(VINCI).  PAVE is a VA directive which requires VA medical centers to track Veterans by their 
risk of future lower extremity amputation. VINCI can provide lists of veterans that meet 
eligibility criteria using data from the electronic medical record. We will use the PAVE 
administrative codes and data from VINCI to identify potential participants. We will use multiple 
recruitment modalities including, but not limited to, recruitment through providers in Podiatry 
clinics, individual letters, posters in key clinics, electronic bulletin boards and My HealtheVet. 
We will track how participants heard about the study at enrollment in order to focus on the most 
successful recruitment modalities. 
6.1.1 Distribution of IRB approved informational flyer 
Study staff will distribute an IRB approved informational flyer/letter about the study to 
eligible potential participants and provide a phone number for follow-up. Study staff will 
approach eligible participants about participation using the following script. 
 
Hello, my name is INSERT NAME HERE.  I am a researcher with the Baltimore VA MC.  I am 
part of a research team conducting a study on how to prevent foot ulcers in people with diabetes.  
You may be eligible to participate in the study.  Would you like to hear more about it? 
 
If NO, say the following: 
Thank you for your time. 
 
If YES, say the following: 
The study is about how to prevent foot ulcers in people with diabetes through using a special 
wipe to clean your feet each day. You would have seven study visits over a little more than 1 year 
in which we will gently brush your feet with a swab like a Q-tip. This study will tell us whether 
using study cloth wipes prevents foot ulcers. 
 
Are you interested in hearing more about the study? 
 
If NO, say the following: 
OK.  Thank you for your time. 
 
If YES: 
Take the participant to a private space where no one can easily hear the conversation. Assess 
eligibility criteria and if eligible begin the informed consent process. If the participant is eligible 
and interested, but wants to take the consent home to review, make plans to follow-up with the 
potential participant. 
 
 
Study staff will distribute an IRB approved informational flyer/letter about the study to 
VA providers.  This flyer can be used to remind providers who may be eligible and how to refer 
potentially interested patients to us. 
6.1.2 Mailing of an Introductory letter and an opt out card 
Study staff will mail introductory letters to eligible participants to alert them about their 
potential eligibility for the study.  They will also include an opt out card for potential participants 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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to return if they are not interested and do not wish to be contacted about the study.  If study 
personnel do not receive the opt-out card from potential eligible participants, study personnel 
may contact the potentially eligible participants by phone. 
 
6.2 
Informed Consent 
If the participant is willing to hear more about the project, study staff will verbally review 
the information on the IRB approved informational flyer. If the participant is interested, the study 
staff will schedule an in-person consent or a remote consent date.  For in-person consent, the 
combined written informed consent/ HIPAA form will be discussed with the potential participant 
in a private area. For both in-person consent and remote consenting the potential participant will 
be asked if he/she wishes for study staff to read the consent form verbatim or to summarize it as 
he/she follows along. Potential participants will be asked a series of questions about the study to 
assess whether they understand what is involved in being in the study. Participants must answer 
all questions correctly in order to consent. Participants being consented remotely will be 
provided with 2 consent forms. The participant must sign and date both.  They must either scan 
or take a picture of the signed consent page and transmit it to us using a VA approved Secure 
messaging program or they must mail one of the consents to us via the US postal service. The 
current approved messaging programs for transmitting documents with PHI/PII securely are 
Azure RMS or My HealtheVet Secure Messaging program. For participants being consented 
remotely, the enrollment visit may be split into 2.  During the first part, the participant will be 
consented. The second part, remaining research procedures, will occur soon after the signed 
consent is received by the research team. 
7 
Study Intervention 
Study participants will be assigned to our two experimental groups (chlorhexidine and 
placebo) using a blocked randomization with a 1:1 allocation ratio and variable block size at the 
time the participant returns for Visit #2 and agrees to continue participating in the study. The 
blocking will help assure that our study is balanced over time on the number of chlorhexidine 
and placebo participants. Participants randomized to the intervention will wash their feet using 
SAGE 2% CHLORHEXIDINE GLUCONATE CLOTHS to wipe down their feet each day and 
then apply supplied chlorhexidine-compatible over-the-counter moisturizer. The use of 
moisturizer is part of standard foot care for diabetes. Participants randomized to the control 
group will do the same except they will use SAGE COMFORT BATH CLOTHS which are the 
same cloths but do not contain chlorhexidine. The cloths will be matched in packaging, feel and 
smell to ensure a double blind.  
 
The intervention will be stopped if the participant is felt to have a safety concern (e.g. 
allergy to study product). Because neither chlorhexidine nor mild soap will worsen wounds with 
inadvertent contact, the intervention can be used on existing wounds and ulcers.  While unlikely, 
it is conceivable that a participant will need to be unblinded during the study.  See the SOP for 
Unblinding a Participant for additional information. 
7.1 
Study Product Description 
7.1.1 Acquisition 
SAGE 2% CHLORHEXIDINE GLUCONATE CLOTHS, SAGE COMFORT BATH 
CLOTHS and a chlorhexidine-compatible over-the-counter moisturizer will be shipped to the 
research offices of the principal investigator. 

Preventing Diabetic Foot Ulcers through Cleaner Feet 
 
 
 
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7.1.2 Formulation, Packaging, and Labeling 
SAGE 2% CHLORHEXIDINE GLUCONATE CLOTHS is an FDA-approved medication 
packaged and labeled by SAGE Products Inc.  SAGE 2% CHLORHEXIDINE GLUCONATE 
CLOTHS is packaged with two 7.5in x 7.5in cloths to a package (3 sets of 2 cloth packages 
come bundled together). The product will be repackaged and labeled in a blinded fashion with 
seven cloths per package by study staff using a process that has been approved by the Baltimore 
VA investigational pharmacy. 
SAGE COMFORT BATH CLOTHS contains eight 7.5in x 7.5in cloths soaked in mild, 
rinse-free cleansers and skin-protecting moisturizers like aloe and vitamin E per package. The 
product will be repackaged and labeled in a blinded fashion with seven cloths per package by 
study staff using a process that has been approved by the Baltimore VA investigational 
pharmacy. 
The chlorhexidine-compatible over-the-counter moisturizer will be in its original 
packaging. 
7.1.3 Product Storage and Stability 
SAGE 2% CHLORHEXIDINE GLUCONATE CLOTHS and SAGE COMFORT BATH 
CLOTHS will be stored between 20-25C (68-77F), as directed by the manufacturers. The 
chlorhexidine-compatible over-the-counter moisturizer will be stored with the cloths.  The study 
products (cloths and moisturizer) will be stored in a locked room in either a research office of the 
principal investigator or the Baltimore VA GRECC in a manner approved by the Baltimore VA 
investigational pharmacy. 
7.2 
Dosage, Preparation and Administration of Study Intervention 
The cloths and moisturizer will be applied by the participant or caregiver once daily.  
7.3 
Modification of Study Intervention 
If a participant develops signs of intolerance to either cloth or chlorhexidine-compatible 
over-the-counter moisturizer, they will be stopped, and the reaction evaluated. Signs of 
intolerance include generalized redness, persistent itching, or swelling of the feet in the absence 
of other identifiable causes. The VAMHCS will provide treatment as appropriate and the 
participant will return for evaluation. If clinically appropriate and the participant is willing, we 
will start a lower dose (e.g., wipe every other day) and reevaluate. If problem recurs, discontinue 
use of wipes. If problem does not recur increase to full dose. If problem recurs on full dose, 
repeat and keep on reduced dose. 
7.4 
Accountability Procedures for the Study Intervention 
The PI is responsible for ensuring that a current record of product disposition is 
maintained, and product is dispensed only at an official study site by authorized personnel as 
required by applicable regulations and guidelines.  
SAGE 2% CHLORHEXIDINE GLUCONATE CLOTHS/ SAGE COMFORT BATH 
CLOTHS and chlorhexidine-compatible over-the-counter moisturizer will be distributed to 
participants by trained study staff members.  Documentation of all products received, distributed 
and destroyed will be kept by study staff members.  
7.5 
Assessment of Participant Compliance with Study Intervention 
Instructions regarding dosing, missed doses and possible side effects will be provided. 
Adherence with cloths will be measured by 1) using chlorhexidine measurement of the skin from 

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15
non-invasive swabs of foot skin during each study visit, 2) counting remaining wipes in returned 
cloth wrappers and 3) having participants check off use on a monthly calendar. All will be 
returned to the study team during the in-person study visits. Participants doing remote study 
visits will report their number of remaining wipes over the phone, return their completed 
monthly calendars , and one additional bag of wipes will be prepared for each shipment to test 
confirmation of cloth type (chlorhexidine vs. placebo) 
8 
Study Procedures/Evaluations 
 
Visit # (approx. weeks) 
1  
(0) 
2  
(1) 
3 
(13)
4 
(26)
5 
(39)
6 
(52)
7 
(56)
Screen participants and verify inclusion and 
exclusion criteria that can be obtained at that time
 
 
 
 
 
 
 
Review study with participant; administer questions 
to assure participant understands the study and their 
participation within the study.
 
 
 
 
 
 
 
Obtain/Confirm informed consent
Provide information on foot self-care for people with 
diabetes 
 
 
 
 
 
 
 
Confirm all inclusion and exclusion criteria
Randomization
Demonstrate use of cloths and moisturizer and have 
participant or family member demonstrate ability to 
use cloths; monitor for immediate allergic reaction
 
 
 
 
 
 
 
Document current foot conditions, past foot 
conditions, usual foot self-care, type of footwear, 
recent antimicrobial use, complications of diabetes, 
control of diabetes and major medical issues 
including functional status from medical record and 
participant interview
 
 
 
 
 
 
 
Record time and date of last time feet were washed.  
Record daily foot washing, drying, and foot lotion 
patterns from the last 4 weeks.
 
 
 
 
 
 
 
Collect a focused history focusing on changes since 
enrollment
 
 
 
 
 
 
 
Complete a brief physical assessment of the culture 
sites
 
 
 
 
 
 
 
Obtain non-invasive skin specimens of nares and on 
each foot (Nares will not be collected if participant 
has respiratory symptoms)
 
 
 
 
 
 
 
Obtain photographs of each foot
Distribute SAGE 2% CHLORHEXIDINE 
GLUCONATE CLOTHS or SAGE COMFORT 
BATH CLOTHS and chlorhexidine over-the-counter 
compatible moisturizer daily x12 months
 
 
 
 
 
 
 
Reconfirm participants willingness to participate
Assess chlorhexidine levels on the feet using a non-
invasive swab
 
 
 
 
 
 
 

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16
 
Visit # (approx. weeks) 
1  
(0) 
2  
(1) 
3 
(13)
4 
(26)
5 
(39)
6 
(52)
7 
(56)
Assess adherence with cloths participant diary, and 
counting all cloth wrappers (empty, partially filled or 
unused)
 
 
 
 
 
 
 
Query participants for adverse events
Physical assessment of the feet. Document 
development of a new foot ulcer or foot infection or 
other foot conditions. Document healing of existing 
foot wounds.
 
 
 
 
 
 
 
Encourage adherence in use of study medication 
with up to weekly texts/phone calls
 
Up to weekly 
 
Call/text participant to inquire if any new concerns 
regarding foot health have developed
 
Monthly 
 
Medical record review for foot ulcers, infection or 
amputation; record clinical management of ulcers, 
infection or amputation
At week 52; participants with 
ulcers will be followed for 
additional 90 days if needed
 
8.1 
Study Visits 
 
Study visit windows are as follows: 
 Study visit #2 will occur 1 week after enrollment with a window of 3 to 28 days.  
 Study visit #3 will occur 12 weeks after study visit #2 with a window of 5 to 18 weeks. 
 Study visit #4 will occur 25 weeks after study visit #2 with a window of 19 to 31 weeks. 
 Study visit #5 will occur 38 weeks after study visit #2 with a window of 32 to 44 weeks. 
 Study visit #6 will occur 51 weeks after study visit #2 with a window of 45 to 53 weeks. 
 Study visit #7 will occur at least 2 weeks after visit #6 or after they stop using study 
wipes. For participants who were randomized and self-withdraw or are randomized and 
are withdrawn from the study by study staff, visit #7 can occur at least 2 weeks after they 
stop using study wipes. 
 
The participant interview portion of the study visit will be conducted by phone if participants are 
not able to make it into the VA during their scheduled visit. Participants that wish to do visits 
remotely will be asked to swab their feet and mail it to the lab. They will also be asked to take  
pictures of their feet and transmit it to study staff to assess foot health. 
 
Missed visits will not be reported as deviations. 
 
Participants will either be texted or called weekly, depending on the participant’s preference as a 
reminder to use study medication.  Participants who prefer to receive weekly reminder texts will 
have the option to receive them from the Annie App. The Annie App is a new VA approved 
texting program that provides a full audit trail of all text communications with participating 
veterans. We will also call participants monthly to assess foot health. Participants will also be 
encouraged to call if they have foot related issues.  In the event there is a foot related issue, we 
will facilitate a visit to podiatry at the VAMHCS. 

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8.2 
Laboratory Evaluations 
During each study visit a specimen is obtained by trained research personnel from each of 
the following sites: anterior nares, and up to eight more swab areas on the feet.  If a participant 
has an existing full thickness area of skin breakdown on one of the foot skin sites, research 
personnel will not obtain a specimen from that site. These specimens are tested for S. aureus and 
microbial burden using microbiological and PCR based methods and are also analyzed for the 
presence of all bacteria using metagenomics techniques.  The swabs from visit # 2, #3, and #7 
will be cultured for specific pathogens (E. spp., Staphylococcus aureus, Klebsiella pneumoniae, 
Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium and diabetic 
foot infection pathogens) as well as E. coli, Streptococcus, and Enterococcus faecalis. Minimum 
inhibitory concentrations to chlorhexidine and to key antibiotics. 
8.3 
Clinical Evaluations 
There will be a physical assessment of the feet at each study visit as well as photographs 
taken of the feet. Medical records will be reviewed to document the presence of new foot 
complications. 
9 
Unanticipated Problems and Serious Adverse Events  
We will follow the reporting requirements specified in the VHA Handbook 1058.01.  We 
will collect all of the information required to follow those reporting requirements. Reportable 
New Information2 will be reported to the IRB within 5 business days. 
10 Quality Control and Quality Assurance 
The PI and affiliated institution are responsible for conducting the study in compliance 
with the IRB-approved protocol, all applicable federal and state regulations, VHA Handbook 
1200.05 Requirements for the Protection of Human Subjects in Research and the International 
Conference on Harmonization, E6 Good Clinical Practice by adhering to the requirements for 
collecting, documenting and reporting complete and accurate data.  A separate Data Quality 
Assurance Plan will be developed for this protocol to describe the frequency of review of study 
related data and the roles and responsibilities for activities related to Quality Control.   
11 Statistical Plan 
11.1 Analysis Plan 
Primary objective: We hypothesize that the chlorhexidine group will have longer times to new 
foot complication event (chronic foot ulcer, foot infection, or foot amputation) than the placebo 
group. We will non-parametrically describe the distribution of “survival” times, from 
randomization until foot complication, in each group with a Kaplan-Meier curve as well as 
calculate the 75th percentile and median survival time, if possible. The log-rank test will test the 
null hypothesis of no difference in the distribution of times to foot complication between the two 
arms.  In primary analyses, death will generally be treated as a non-informative censoring 
mechanism.  Secondary analyses using more sophisticated models (e.g. Cox regression, partial 
competing risks model) will be utilized if there are significant prognosticator imbalances, death 
rates, or interval censoring Adherence with treatment will be examined as a potential moderator 
using Cox regression. A participant’s medical chart will continue to be monitored for trial 
outcomes even if the patient stops participating in treatment (chlorhexidine or placebo) unless 
 
2 http://www.umaryland.edu/media/umb/oaa/hrp/documents/study-tools-docs/Reportable-New-Information_6-28-
11.pdf 

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the patient withdraws consent for the study to continue to review their medical chart.  Hence, 
generally the primary analysis will be intent-to-treat.   For planning a larger clinical trial, we will 
also estimate the hazard ratio of new foot complications for chlorhexidine versus placebo with a 
95% confidence interval.   
Secondary objective: We hypothesize that a) the chlorhexidine group will not be colonized with 
Enterobacter spp., S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa and E. faecium 
(ESKAPE) and diabetic foot infection pathogens with a higher minimum inhibitory 
concentration (MIC) to chlorhexidine than the placebo group. All study participants colonized 
with pathogens at the V7 time point will be included in the primary analysis. The null hypothesis 
of no difference in MIC distribution will be tested with the nonparametric Wilcoxon Rank Sum 
test due to the range-limited, discrete distributions of MICs. Effect sizes will be expressed in 
terms of means on a log(2) scale because the mean as an effect size metric will be more sensitive 
to group differences than the median. In addition, we will compute 95% confidence intervals 
around effect size estimates to quantify the precision of estimates. 
Exploratory objective: This objective is not hypothesis driven. We will explore the impact of 
chlorhexidine on the diversity of the skin microbiota of the feet and the impact of the diversity of 
the skin microbiota on the development of new foot complications. 
11.1 Sample Size Calculation 
How many participants (or specimens, or charts) will be used in this study? 
Local: 200    Worldwide: 200 
 
Sample size is based on the primary objective and outcome.  We will test the null hypothesis for 
the primary objective that there is no difference in time to new foot complication between the 
control and intervention groups using a log-rank test (two-tailed, 5% significance level).  We 
assume that 10% of participants will die prior to one year of follow-up. We used the Freedman 
method for sample size calculation reported in Machin et al. (1997) using NCSS PASS software 
(2011).  Prior data suggest that the annual proportion of individuals with new foot complications 
among controls will be about 0.4. If the true proportion for experimental participants is 0.2 one 
year after randomization, power of the log-rank test will be 0.82 to detect the difference if 100 
patients are randomize to each study arm (i.e. total N=200).  
12 Ethical Considerations 
This study will be conducted according to US and international standards of Good Clinical 
Practice (FDA regulations 21 CFR 312 for IND studies and FDA guidance E6) for all studies.  
Applicable government regulations, VHA Handbook 1200.05 Requirements for the Protection of 
Human Subjects in Research and UMB research policies and procedures will also be followed. 
All participants for this study will be provided a consent form describing this study and 
providing sufficient information for participants to make an informed decision about their 
participation in this study.  This consent form will be submitted with the protocol for review and 
approval by the IRB.  The formal consent of a participant, using the IRB-approved consent form, 
will be obtained before that participant is submitted to any study procedure.  This consent form 
must be signed by the participant, and the investigator-designated research professional obtaining 
the consent.  
13 Data Collection, Handling and Storage 
 The Principal Investigator is responsible to ensure the accuracy, completeness, legibility, 
and timeliness of the data reported.  Data collection is the responsibility of the study staff. All 

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study personnel will be current in Information Security Training (VHA Privacy and Information 
Security and Rules of Behavior Training). 
Paper records or case report forms will be filled out at the participating clinical sites or in 
the research team offices. Copies of the paper records or case report forms will serve as source 
documents and maintained for recording data for each subject enrolled in the study.  All source 
documents will be completed in a legible manner to ensure accurate interpretation of data.  When 
making changes or corrections, the original entry will be crossed out with a single line, and the 
change initialed and dated.  Erasing, overwriting, or use of correction fluid or tape will not be 
done. 
All source documents and laboratory reports will be reviewed by the clinical team and data 
entry staff, who will ensure that they are accurate and complete.  AEs must be graded, assessed 
for severity and causality, and reviewed by the site PI or designee.  
Confidentiality will be maintained to the extent permitted by law. Research records 
generated in this study will be transported from clinical protocol study site to data entry site by 
study personnel, accompanied by an Authorization to Transport and Utilize VA Sensitive 
Information Outside Protected Environments. Data will be maintained on a secure electronic 
central database on a VA research server (OITBALFPCRSCH01). Identifiable electronic study 
data will never be removed from behind the VA firewall. Analysis of identifiable study data will 
be performed only behind the VA firewall. Data will be backed up according to the VA network 
back up schedule.  Paper records will be stored in locked filing cabinets behind a locked door in 
office space at the University of Maryland Baltimore that is accessible to the study PI. 
Identifiable records at UMB will only be accessible by VAMHCS staff on VA time. Study 
personnel who leave the research team will have their access to study data removed immediately. 
If data is lost/stolen, the VAMHCS, ISO/PO/PI and the UMB IRB will be notified immediately. 
A unique identifier or code will be assigned to each participant. Bacterial isolates and culture 
specimens and datasets used for analysis will be labeled with this code instead of the subject 
name or SSN. There will be no identifiable data on any of the samples or data sent to the UMB 
microbiology lab. Only the study personnel who directly interact with subject or manage the 
subject’s clinical protocol data will have access to participant identifying information, which will 
be kept behind the VA firewall on the OITBALFPCRSCH01.VA05.med.va.gov server, in the 
folder \\\roghmann_share\Diabetic Foot Clinical Trial_HP79894\Databases\Main Study 
Database. Culture data will be entered directly into the relational database; however, 
microbiology laboratory personnel will not have access to participant identifiers in the database. 
Microbiological samples will be transferred to Dr. Roghmann’s VA lab (Baltimore VA Medical 
Center, Microbiology Research Lab, 3C-112) on an ongoing, regular basis (approximately 
quarterly). The Principal Investigator will maintain all records pertaining to this study according 
to Records Control Schedule 10-1. As soon as permitted and when data collection is complete - 
source documents will be shredded and identifying information (names/SSN) will be removed 
from the database. There will be a single data table which maintains the link between the unique 
code and patient identifiers. This table will be maintained on a VA server. As soon as permitted 
and when data collection is complete, the link between code and identifying information will be 
deleted on the server and in any backups. If any paper copies of the link have been made, they 
will be shredded. 
 
14 VA Informatics and Computing Infrastructure (VINCI) 
The VA Informatics and Computing Infrastructure (VINCI) is a major informatics initiative of 
the Department of Veterans Affairs (VA) that provides a secure, central analytic platform for 

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performing research and supporting clinical operations activities. It is a partnership between the 
VA Office of Information Technology (OI&T) and the Veterans Health Administration Office of 
Research and Development (VHA ORD). VINCI includes a cluster of servers for securely 
hosting suites of databases integrated from select national VA data sources. VINCI servers for 
data, applications and virtual sessions are physically located at the VA Austin Information 
Technology Center (AITC), located in Austin, Texas. This secure enclave with 105 high-
performance servers and 1.5 petabytes of high-speed data storage has multiple layers of security 
and disaster recovery to prevent data loss. 
 
To ensure the protection of Veteran data, VINCI maintains compliance with the guidelines set 
forth by Veterans Health Administration (VHA) Handbook 1200.12, Use of Data and Data 
Repositories in VHA Research, and all other applicable VA and VHA policies and regulations. 
In addition, VINCI has undergone all security certification activities in support of obtaining an 
Authorization to Operate (ATO). Access to VINCI resources are approved in accordance with 
the requirements of National Data Systems (NDS), VHA Handbook 1200.12, Use of Data and 
Data Repositories in VHA Research, and all other applicable VA and VHA policies and 
regulations. All data transferred from VINCI is subject to audit for compliance. 
 
VA-credentialed research or operations staff are granted access to study-specific data along with 
tools for analysis and reporting in the secure, virtual working environment through a certified 
VHA network computer within the VA.  If not working within a VA or VHA hosted office 
environment containing VA network access, researchers may apply for and then access VINCI 
through an approved Virtual Private Network (VPN) and Remote Desktop application. The 
remote computing environment enables data analysis to be performed directly on VINCI servers, 
offering a number of advantages: uniform security standards for access; a common point of entry 
for all investigators who use the data; tools for analysis and reporting; tighter and more 
consistent control of data quality; and the ability to standardize and update terminology and 
format as technology and methodology improve.  
 
Data Collection 
VA provides care to Veterans at over 1,400 points of care. At the core of virtually all care 
processes is a broadly scoped and extensively used electronic health record system known as the 
Veterans Information System Technology Architecture (VistA). VistA provides a longitudinal 
view for patients receiving care nationwide including diagnoses, procedures, medications, labs, 
physiologic measurements, and text notes and reports. VA uses 130 VistA implementations to 
provide electronic health record services nationwide for just over 20 million Veterans 
historically. The aggregate content of these 130 VistA systems includes 2.3 billion documents 
(e.g., Progress Notes, Discharge Summaries, Reports) accumulating at a rate of 696,000 each 
day; 6.2 billion lab values (+1.5 million each day), 3.4 billion orders (+845,000 each day), and 
1.7 billion medication administrations and prescription fills (+390,000 each day). 
 
Data are aggregated from individual VistA systems to the VA Corporate Data Warehouse where 
it is modeled and prepared for use. Data published by the VHA Decision Support System (DSS), 
Inpatient and Outpatient Medical SAS (MedSAS), VA Health Economics Resource Center 
(HERC) cost data, Vital Status and VA-CMS linked data files maintained by VA Information 
Resource Center (VIReC), CDC National Death Index VA-linked data, and several other 
specialty data sets can be requested through VINCI. VA National Data Services and other data 
stewards regulate the right to use the data, but VINCI facilitates the process. When study 

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requests are approved, project-specific data are extracted from source databases and placed in 
SQL tables accessible only to the research team and VINCI data managers. 
 
Storage of Study Data 
Study data will be kept in accordance with the Department of Veterans Affairs Record Control 
Schedule 10-1 (RCS 10-1). Storage and transfer of any Personally Identifiable Information (PII) 
or Protected Health Information (PHI) must be done in accordance with applicable VA and VHA 
policies and directives, state and federal regulations, and applicable statutes including the Health 
Insurance Portability and Accountability ACT (HIPAA). Unless explicitly requested and 
approved by data stewards, all sensitive patient data must remain on VINCI project servers and 
only aggregate data without PII / PHI may be transferred from VINCI. Any desired change in 
data storage location or transfer requires amending the original data request with an updated of 
disposition of study data. The amendment must be approved by all data stewards before data may 
be transferred.  
 
Violations of data policy or approved use of data will be subject to full penalty of law, which 
may include suspension of access privileges, reprimand, suspension from work, demotion, 
removal, and criminal and civil penalties. 
 
Upon completion of the research project, the study principal investigator in conjunction with the 
VA Information Security Officer (ISO), and in accordance with VA policy, will ensure that, 
study data containing sensitive, confidential information will be returned to the VA, sanitized 
and removed from all servers, desktops, removable storage devices, etc. 
 
Data Access 
Only study team personnel explicitly authorized by data stewards will have access to project 
data. The study principal investigator has the responsibility for security of study. VINCI data 
managers and VA OI&T personnel not under the purview of the study principal investigator 
control the servers, network, processors, firewall and software in the VINCI environment, 
including access rights granted to study personnel. 
 
When study personnel are no longer part of the research team, the study principal investigator 
will amend the data access request to terminate that person’s access to all study data and notify 
the VA Information Security Officer of such action. No sensitive patient data may be shared with 
anyone who does not have a VA appointment. All study team personnel with access to sensitive 
patient data must stay current on required VA information security and privacy policy trainings. 
 
Data Storage Location 
Study data stored on VINCI servers is located at the Austin Information Technology Center, 
1615 Woodward St., Austin, TX 78772-0001. The specific server where the data are stored 
within the VINCI environment will be chosen by VINCI personnel. The server name and 
location within the Austin Information Technology Center may be changed at any time at the 
discretion of VINCI personnel. 
 
Specialized Software 
All software used to access sensitive patient data, whether provided by VINCI, or developed by 
the study team, will run in virtual desktop sessions on VINCI servers within the Austin 
Information Technology Center. 
 

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15 Chesapeake Regional Information System for our Patients (CRISP) 
CRISP is a regional health information exchange serving Maryland and the District of Columbia. 
The CRISP Portal is a free tool available to clinical staff. As clinical information is created and 
shared with CRISP, it is made accessible in real time to participating health providers through 
the CRISP Portal.  The portal gives providers the ability to securely look up patient information 
though the internet.  CRISP allows physicians and other authorized people to see healthcare 
activity at other hospitals. For this study, if an enrolled veteran seeks healthcare outside of the 
VA, researchers will be able to review the records in CRISP for that care to determine the study 
outcome.  Identifying information for study participants will be securely transmitted between 
study personnel and CRISP using FIPS 140-2 validated encryption during transmission. 
 
 

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APPENDIX: Study variables 
Variables 
How Ascertained 
PARTICIPANT CHARACTERISTICS (measured once on each subject at 
Enrollment)
Name
CPRS
SSN
CPRS
Street address
Participant response
Phone number
Participant response
Email address and/or cell phone
Participant response
Demographics 
Age
CPRS
Sex
CPRS
Race
CPRS
Ethnicity
CPRS
Most recent height and date measured
CPRS
Most recent weight and date measured
CPRS
Able to use wipes for foot care
Participant response
Plan to reside in the area for the next 13 months
Participant response
Ability to walk
Participant response
Requires equivalent of institutional care
CPRS
Smoking status
Participant response
People in participant’s household
Participant response
Health Conditions 
Diagnosis of diabetes
CPRS
Diabetes medication
CPRS
Year diabetes diagnosed
Participant response
Type of footwear used
Participant response
Presence of left foot
CPRS
Presence of right foot
CPRS
Current infection on either foot
CPRS/Foot photographs
Current foot ulcer, wound or unhealed amputation 
on left foot, date of diagnosis, size, location on foot
CPRS/Foot photographs 
Current foot ulcer, wound or unhealed amputation 
on right foot, date of diagnosis, size, location on foot
CPRS/Foot photographs 
Dates of healing of healed foot ulcers, wounds, 
infections and toe or transmetatarsal amputations 
(most recent captured for each)
CPRS 
Amputation of the foot planned to treat current foot 
ulcer or wound
CPRS 
Current preulcer lesion on either foot
CPRS/Foot photographs
Use of topical chlorhexidine or other topical 
antimicrobial agent on feet in past 7 days and in the 
past 12 months
Participant response 
Use of systemic antibiotic in the past 3 months
CPRS
History of an allergic reaction to chlorhexidine
CPRS
Life expectancy >12 months
CPRS
Foot deformity/surgery
CPRS/Foot photographs

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Variables 
How Ascertained 
Diabetes related co-morbidities such as PVD, 
congestive heart failure, etc
CPRS 
Foot characteristics such as Charcot deformity and 
onychomycosis, etc
CPRS/Foot photographs 
Current medications
CPRS
Visual acuity and retinopathy from most recent eye 
exam
CRPS 
Lab Values at Enrollment 
Most recent HbA1c, date collected (also collected at 
subsequent study visits)
CPRS 
Most recent LDL, date collected
CPRS
Most recent HDL, date collected
CPRS
Most recent creatinine, date collected
CPRS
Most recent total cholesterol, date collected
CPRS
VARIABLES COLLECTED AT EACH VISIT
Currently smoke
Participant response
Frequency of foot washing with soap and water in 
past 4 weeks
Participant response 
Frequency of foot washing with a washcloth in past 
4 weeks
Participant response 
Frequency of drying between toes in past 4 weeks
Participant response
Frequency of using lotion on feet in past 4 weeks
Participant response
Date and time of last foot washing
Participant response
Use of antimicrobials (other than study medication) 
since last study visit, dates of use
CPRS and participant 
response
Use of chlorhexidine wash on feet during podiatry 
visit
CPRS 
Symptoms of allergic reaction to study medication
Participant response
Adherence to study medication 
Participant adherence diary 
and count opened wipe 
packages
Development of a new foot ulcer
CPRS
Development of a new foot infection and if related 
to existing ulcer at randomization
CPRS 
New foot amputation and if related to existing ulcer 
at randomization
CPRS 
Healing of all foot ulcers, wounds, and unhealed toe 
or transmetatarsal amputations present at enrollment
CPRS 
Nose and foot colonization results
Culture
Nose and foot microbiome results
Culture
Chlorhexidine level on foot skin
Culture
VARIABLES COLLECTED AT EACH ‘AT HOME’ VISIT
Symptoms of allergic reaction to study medication
Participant response