Characterization of AmnioExcel Plus in Two Treatment Paradigms
Phase: NA
Conditions: Diabetic Foot Ulcer
Sponsor: University of Texas Southwestern Medical Center

 
 
Official title: Characterization of AmnioExcel Plus in two treatment 
paradigms 
 
NCT number: NCT04233580 
IRB Approved date: 08/11/2020 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
1 
vMar2018 
PROTOCOL FORM / RESEARCH DESCRIPTION 
 
If an item does not apply to your research project, indicate that the question is "not applicable” – do not leave sections blank 
 
Click once on the highlighted entry in each box to provide your response.  Click the item number/letter or word, if hyperlinked, 
for detailed instructions for that question.  If your response requires inserting a table, picture, etc, you may need to first delete the 
box that surrounds the answer and then insert your table or other special document. 
 
 
1.  Purpose and objectives.           List the purpose and objectives: 
 
There is a worldwide epidemic of diabetes. Foot ulcers are one of the most common complications in diabetic patients leading to 
amputation and hospitalization. The identification of biomarkers to determine which patients will heal and those that need more 
extensive intervention is critical to improve healing outcomes. The purpose of this study is to evaluate two different application 
paradigms with AMNIOEXCEL Plus® in Diabetic Foot Ulcer.  The study will further characterize AE+ in wound healing outcomes 
and assess the role of aggressive debridement in wound healing outcomes.  Study outcomes include 
• 
Incidence of healing at 12 weeks 
• 
Percent area reduction 
• 
Percent volume reduction 
• 
Level and type of Debridement 
• 
Wound bed perfusion (hyperspectral imaging) 
 
 
2.  Background. 
• 
Describe past experimental and/or clinical findings leading to the formulation of your study.   
• 
For research involving investigational drugs, describe the previously conducted animal and human studies.   
• 
For research that involves FDA approved drugs or devices, describe the FDA approved uses of this drug/device in 
relation to your protocol.   
• 
Attach a copy of the approved labeling as a product package insert or from the Physician’s Desk Reference.   
You may reference sponsor’s full protocol or grant application (section number and/or title) or if none, ensure background 
includes references. 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
a. 
Background 
The overall objective of this pilot study is to evaluate the use of AMNIOEXCEL Plus® to heal diabetic foot wounds. Failure of 
a wound to heal in an organized and timely fashion is complex and multifactorial. Chronic wounds are characterized by a 
persistent inflammatory state resulting from local wound factors such as necrotic tissue, high microbial burden, low oxygen, 
and repetitive injury. Also, diabetes associated metabolic co-morbidities, especially peripheral arterial disease (PAD) and 
hyperglycemia, contribute to the persistence of chronic wounds.  Treatments include re-vascularization, wound debridement, 
pressure off-loading, glycemic control, and modification of patient behaviors, such as tobacco abuse and compliance with off-
loading devices.  
 
b. 
Current practice 
Human amniotic membrane (AM) has been widely applied in the management of burns, dermatological defects and ocular 
surface reconstruction.  AMNIOEXCEL Plus® is a human placental-based tissue consisting of dehydrated, tri-layer Placental 
(Amnion/Chorion/Amnion) Allograft Membrane (T-PAM) layers. T-PAM is a minimally manipulated placental membrane 
product intended for homologous use for the repair, reconstruction and replacement of skin at the direction of a physician. 
AMNIOEXCEL Plus contains Human Cellular and Tissue Based Products (HCT/P) as defined by US FDA 21 CFR Part 1271.  
It has been estimated that 15% of diabetics will have a lower extremity ulcer in their lifetime. In the United States there are 
approximately 120,000 non-traumatic lower extremity amputations performed each year. The direct cost of foot ulcers and 
amputations has been conservatively estimated to be approximately 1.6 billion dollars a year without consideration for 
physician fees, prosthetics, or rehabilitation costs.  
 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
2 
vMar2018 
 
3.  Study Design.  
Describe the study design (e.g., single/double blind, parallel, crossover, etc.)  Consider inserting a scheme to visually present the 
study design. 
 
We plan to evaluate healing in two cohorts of patients with diabetic foot wounds (n=20) that receive optimal treatment including 
serial wound debridement and off-loading with a boot or postop shoe and AmnioEXCEL+. In one cohort, AmnioEXCEL+ will be 
applied weekly at study visits and in the second cohort, AmnioEXCEL+ will be applied maximum every 2 weeks (PRN, in the 
case that the wound requires debridement at a visit not intended for AE+ application, the wound will be treated as SOC). In 
addition, we will collect data on other potential confounding factors that could affect healing such as antibiotic, anti-fungal and 
anti-infective medications, tobacco, comorbidities, diabetes control, infection, perfusion, and activity. Wound healing, including 
wound size and adverse events will be evaluated. 
 
 
4.  Research Plan / Description of the Research Methods:   
4.a.  Provide a comprehensive narrative describing the research methods.   
     1) Provide the order in which tests/procedures will be performed,  
     2) Provide the setting for these events and a description of the methods used to protect privacy during the study.   
     3) Provide the plan for data analysis (include as applicable the sample size calculation) 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
Subjects will be identified by the PI or Sub- from the investigators' clinic schedule. We plan a prospective cohort study of 40 
diabetic patients with foot ulcerations treated at Parkland foot wound clinic and UTSW wound clinic.  
 
The PI, Sub-I, or study coordinator will carefully review this research study with the subject in a private area and any family 
members or caregivers. Any questions will be answered, and it will be emphasized that participation in the research is voluntary. 
When all questions are answered, and the subject has agreed to participation in the research, the subject will sign the Consent 
and HIPAA Authorization.  The subject will receive a copy of the signed documents. Subjects will be enrolled based on basic 
inclusion/exclusion criteria. Subject will be given ample time to consider.  
 
Study Procedures: 
 
Collection of Demographic data, medical/social history 
Collection of medications1 
Ankle Brachial Index2 
Wound debridement3 (standard of care procedure) and tissue collection of normally discarded tissue of up to 3 samples on 
Baseline visit and weeks 3, 6, and 9.  
Imaging with eKare4 
Hyperspectral Imaging 
Application of study product 
 
1Only collect antibiotics, anti-fungal and anti-infective medications.  
2 ABI (with toe pressure) can be done at screening or baseline. 
3 Once wound is healed, wound debridement will not be done at weekly visits.  
4 Once wound is healed, eKare will not be done at weekly visits. 
5 EOS will occur on the date the subject is healed. 
*Screening and Visit 1 may be done on the same day. 
 
Screening and Enrollment*: 
• 
Review and sign the Informed Consent and HIPAA Authorization 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
3 
vMar2018 
• 
Review the inclusion and exclusion criteria 
 
If the subject qualifies for the study, they will participate in the following procedures (weekly visits, +/-4 days): 
 
Visit 1*:  
• 
Demographics (such as age, gender, race or ethnicity) 
• 
Past Medical History, Social History, Medications documented. 
• 
Labs documented as SOC within 6mo of initial visit 
• 
ABI with toe pressures2 
• 
Wound debridement and collection (3 samples) of discarded tissue from debridement  
• 
eKare wound measurement 
• 
Hyperspectral Imaging 
• 
Randomization 
• 
Application of AmnioEXCEL+ 
• 
Source documentation 
• 
Stipend disbursement 
 
Visits 2 through 6:  
• 
Wound debridement3 (tissue collection at weeks 3 and 6) 
• 
eKare wound measurement4 
• 
Hyperspectral imaging 
• 
Application of AmnioEXCEL+ per cohort assignment  
• 
Source documentation 
• 
Stipend disbursement 
 
Visit 7:  
• 
Medications documented 
• 
Wound debridement3 
• 
eKare wound measurement4 
• 
Hyperspectral imaging  
• 
Application of AmnioEXCEL+ per cohort assignment  
• 
Source documentation 
• 
Stipend disbursement 
 
Visits 8-11:  
• 
Wound debridement3 (tissue collection at week 9) 
• 
eKare wound measurement4 
• 
Hyperspectral Imaging 
• 
Application of AmnioEXCEL+ per cohort assignment  
• 
Source documentation 
• 
Stipend disbursement 
 
Visit 12:  
• 
Wound debridement3 
• 
eKare wound measurement4 
• 
Source documentation 
• 
Stipend disbursement 
 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
4 
vMar2018 
End of Study (EOS) Visit 5:  
• 
Medications documented 
• 
Wound debridement3 
• 
eKare wound measurement4 
• 
Source documentation 
• 
Subject exit from study 
 
6. Criteria for Inclusion of Subjects: 
• 
Diagnosis of Diabetes Mellitus  
• 
21-90 years of age  
• 
Able to provide informed consent 
• 
Chronic foot ulceration below the ankle – persistent for >30 days  
 
7. Criteria for Exclusion of Subjects: 
• 
<21 or >90 years of age 
• 
Unable to provide informed consent 
• 
History of poor compliance in the opinion of the investigator 
• 
Gangrene 
• 
Untreated osteomyelitis 
• 
Widespread malignancy 
• 
Active alcohol or substance abuse such as cocaine, heroin, or methamphetamines that in the opinion of the investigator 
will impact the subject’s participation in the study 
• 
Pregnancy 
 
The eKare and Hyperspectral Imaging cameras are research-only. Everything else is standard of care. The cameras do not touch 
the patient. 
 
Analysis and Statistical Approaches 
As this study is designed as open-label case series to evaluate different treatment protocols using AmnioEXCEL+.  Descriptive 
statistics will be performed there will be no statistical analysis for this study.  Wound healing outcomes will be assessed in both 
treatment cohorts. 
 
The eKare and Hyperspectral Imaging cameras are research-only. Everything else is standard of care. The cameras do not touch 
the patient. We will collect up to 3 samples of discarded tissue from debridement at Baseline and weeks 3, 6, and 9 if applicable. 
This is the standard of care debridement and tissue that would have been discarded.  
 
 
 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
5 
vMar2018 
 
4.b.  List of the study intervention(s) being tested or evaluated under this protocol 
 
N/A -  this study does not test or evaluate an intervention.    Skip to item 4.d. 
# 
Study intervention(s) being tested or evaluated under the protocol 
 
 
 
Add or delete rows as needed 
 
Affiliate 
 
Place a check next to 
institution(s) where the  
intervention will be 
performed 
Local Standard 
Practice?  
Indicate whether the 
intervention is 
considered 
acceptable practice 
locally for applicable 
institutions 
1 
AmnioEXCEL+ will be applied weekly 
☒ UTSW 
☒ Yes 
☒ PHHS 
☒ Yes 
☐CMC 
☐ Yes 
☐THR 
☐ Yes 
☐TSRH 
☐ Yes 
☐ Other: _____ 
☐ Yes 
2 
AmnioEXCEL+ will be applied maximum every 2 weeks (PRN, in the case that the 
wound requires debridement at a visit not intended for AE+ application, the wound will 
be treated as SOC). 
☒ UTSW 
☒ Yes 
☒ PHHS 
☒ Yes 
☐CMC 
☐ Yes 
☐THR 
☐ Yes 
☐TSRH 
☐ Yes 
☐ Other: _____ 
☐ Yes 
 
 
4.c.  Risk:Benefit Analysis of study interventions being tested or evaluated under this protocol 
For each study intervention identified in section 6b above, complete a risk:benefit analysis table. 
 
(Two tables are provided, copy & paste additional tables as needed or delete both tables if this study does not test an 
intervention) 
 
 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
6 
vMar2018 
4.c. 
Study Intervention #1 
AmnioEXCEL+ will be applied   
List each group exposed to this 
intervention on a separate line. 
(e.g., experimental, control, Arm A, Arm B, 
etc) 
Or state All Groups/Subjects 
For each group, list the benefits of this intervention.  (Benefits can be directly from 
the intervention or from a monitoring procedure likely to contribute to the subject’s 
well being).  If there are no benefits, state “none”. 
All Groups/Subjects will receive the AmnioEXCEL+ product. As with most advanced wound care biologics, AmnioEXCEL+ is expensive.  
Participating in this study will allow patients to receive advanced wound care therapy at no cost to them and that they otherwise may not be able 
to afford. Please see product insert for precautions.  
If you are requesting a Waiver of Informed Consent, complete the table below. 
 
If you have a consent form, list the reasonably foreseeable risks in the consent form (and do not complete this section).   
 
List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious). 
(include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms) 
Do not delete frequency.  Frequency must be estimated because it will assist you with determining which adverse events will require 
prompt reporting.   
 
Not serious 
Serious  
Likely 
These risks are expected to occur in 
more than 20 out of 100 subjects. 
• 
 
• 
 
 
Not serious 
Serious 
Less likely  
These risks are expected to occur in 5-
20 subjects or less out of 100 subjects. 
• 
 
• 
 
 
 
Serious 
Rare  
These risks are expected to occur in 
less than 5 subjects out of 100  
 
• 
 
 
 
 
 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
7 
vMar2018 
 
 
4.d. List ALL other research procedures or components not listed in table 4.b. 
        The combination of Tables 4b and 4d should account for all of the research 
procedures that will take place during this study. 
 
Consider grouping similar procedures under a single component (e.g., blood work, CT = safety 
assessments) 
 
 
All procedures/components are listed in 4a.  
# 
Research component 
• 
individual 
procedures 
 
example: 
Eligibility Assessments 
• 
History and 
physical 
• 
Questionnaire 
• 
Laboratory tests 
Add or delete rows as needed 
Column A 
Local Standard 
Practice Indicate the 
number of times each 
procedure will be 
performed as stipulated 
in the research plan that 
would be performed if 
the participant were not 
participating in the 
study. 
Column B 
Research Only  
Indicate the number of times 
each procedure will be 
performed solely for research 
purposes (meaning that the 
participant would not undergo 
the same number of 
procedures or would not 
undergo the procedure(s) at 
the same frequency if they 
were not participating in the 
study) 
Column D 
Risks 
If you are requesting a Waiver of Informed 
Consent, complete the table below. 
 
List the reasonably expected risks for each procedure 
or group of procedures under the following categories 
as appropriate: 
• Serious and likely; 
• Serious and less likely; 
• Serious and rare; 
• Not serious and likely; 
• Not serious and less likely 
1 
Eligibility Assessments 
  Please complete table 
 
 
 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
2 
Research component 
 
 
 
 
 
The eKare and Hyperspectral 
Imaging cameras are 
research-only. Everything 
else is standard of care. The 
cameras do not touch the 
patient. 
Please see 4a. 
The eKare and Hyperspectral 
Imaging cameras are 
research-only. Everything else 
is standard of care. The 
cameras do not touch the 
patient. 
None 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
3 
Insert component 3 here 
 
 
 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
4 
Insert component 4 here 
 
 
 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
 
 

Form A 
IRB # 
STU  2019-1527 
 
STU2019-1527, Lavery, FormA-ResearchProtocol, Mod_5, 08-11-20 
 
8 
vMar2018 
 
5.  Safety Precautions.  (Describe safeguards to address the serious risks listed above.) 
a.  Describe the procedures for protecting against or minimizing any potential risks for each of the more than minimal risk 
research procedures listed above. 
Please see attached product preparation insert for precautions.  
b.  Where appropriate, discuss provisions for ensuring necessary medical or professional intervention in the event of adverse 
events, or unanticipated problems involving subjects. 
Describe here 
c.  Will the safeguards be different between/among groups?   
Yes 
 
No 
If yes, describe here