Study to Evaluate Celliant Diabetic Medical Socks to Increase Tissue Oxygenation and Incidence of Complete Wound Closure in Diabetic Foot Wounds
Phase: NA
Conditions: Diabetic Foot Ulcer
Sponsor: University of Texas Southwestern Medical Center

STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 
Official title: Study to evaluate Celliant diabetic medical socks to 
INCREASE tissue oxygenation and INCIDENCE OF COMPLETE wound 
CLOSURE in diabetic foot wounds 
 
 
NCT number: NCT04709419 
IRB approved date: 01-03-23 
 

STU2020-1386, Lavery, FormA3-ResearchProtocol-v11.08.22, Mod_10, 01-03-23 
 
i 
 
 
 
STUDY TO EVALUATE CELLIANT DIABETIC MEDICAL SOCKS TO INCREASE TISSUE 
OXYGENATION AND INCIDENCE OF COMPLETE WOUND CLOSURE IN DIABETIC FOOT 
WOUNDS 
 
 
 
 
PROTOCOL NUMBER:   
HGX2020-01 
 
 
 
SPONSOR: 
HOLOGENIX, LLC 
17383 SUNSET BOULEVARD, SUITE A420 
PACIFIC PALISADES, CA 90272 
 
 
 
 
 
 
ISSUE DATE:   
NOVEMBER 8, 2022 

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ii 
 
 
SPONSOR SIGNATURE PAGE 
 
 
 
STUDY TO EVALUATE CELLIANT DIABETIC MEDICAL SOCKS TO INCREASE TISSUE 
OXYGENATION AND INCIDENCE OF COMPLETE WOUND CLOSURE IN DIABETIC FOOT 
WOUNDS 
 
 
 
PROTOCOL NUMBER:   
HGX2020-01 
 
SPONSOR: 
HOLOGENIX, LLC 
17383 SUNSET BOULEVARD, SUITE A420 
PACIFIC PALISADES, CA 90272 
 
 
 
 
 
ISSUE DATE:   
NOVEMBER 8, 2022 
 
 
 
Print Name, Title, Company: __________________________________   
 
Signature:  __________________________________   
Date:  __________________ 
 

STU2020-1386, Lavery, FormA3-ResearchProtocol-v11.08.22, Mod_10, 01-03-23 
 
iii 
 
INVESTIGATOR SIGNATURE PAGE 
 
 
STUDY TO EVALUATE CELLIANT DIABETIC MEDICAL SOCKS TO INCREASE TISSUE 
OXYGENATION AND INCIDENCE OF COMPLETE WOUND CLOSURE IN DIABETIC FOOT 
WOUNDS 
 
 
PROTOCOL NUMBER:   
HGX2020-01 
 
SPONSOR: 
HOLOGENIX, LLC 
17383 SUNSET BOULEVARD, SUITE A420 
PACIFIC PALISADES, CA 90272 
 
 
 
ISSUE DATE:   
NOVEMBER 8, 2022 
 
 
 
Site Name:   
 
 
Print Investigator Name:  ________________________________ 
 
Investigator Signature:  __________________________________  Date:  _______________ 
 
 

STU2020-1386, Lavery, FormA3-ResearchProtocol-v11.08.22, Mod_10, 01-03-23 
 
iv 
Table of Contents 
Primary Study Contacts ......................................................................................................... 1 
UT Southwestern Medical Center, Department of Plastic Surgery ................................................................................................ 1 
Parkland Hospital, Department of Plastic Surgery ........................................................................................................................... 1 
Executive Summary ............................................................................................................... 2 
Background and Rationale .................................................................................................................................................................. 3 
Summary of Findings from Previous Studies .................................................................................................................................... 3 
Device Description ................................................................................................................................................................................ 5 
Regulatory Status .................................................................................................................................................................................. 6 
Benefits and Risks ................................................................................................................................................................................ 6 
1. 
Trial Objectives………………………………………………………………………………….. 9 
2. 
Selection and Withdrawal of Subjects………………………………………………………. 9 
Inclusion Criteria:................................................................................................................................................................................... 9 
Exclusion Criteria: ................................................................................................................................................................................. 9 
Withdrawal of Subjects ........................................................................................................................................................................10 
3. 
Clinical Investigation Plan…………………………………………………………………… 11 
Description of Trial Design ..................................................................................................................................................................11 
Investigational Sites .............................................................................................................................................................................11 
Duration of Subject Participation ........................................................................................................................................................11 
Screening and Enrollment ...................................................................................................................................................................11 
Randomization and Blinding Procedure............................................................................................................................................12 
Visit Schedule .......................................................................................................................................................................................12 
Trial Monitoring .....................................................................................................................................................................................23 
Audits and Inspections ........................................................................................................................................................................24 
4. 
Statistical Analyses…………………………………………................................................. 24 
General Statistical Considerations.....................................................................................................................................................24 
Randomization ......................................................................................................................................................................................25 
Analysis Population..............................................................................................................................................................................25 
Sample Size Justification ....................................................................................................................................................................25 
Primary Efficacy Analyses ..................................................................................................................................................................25 
Interim Analysis for the Key Secondary Endpoint ...........................................................................................................................26 
Hierarchical Testing of the VAS Pain Endpoint ...............................................................................................................................27 
Evaluability of Data ..............................................................................................................................................................................27 
Subject Demographic and Baseline Characteristics .......................................................................................................................28 
Additional Efficacy Analyses including Subgroup Analyses ...........................................................................................................28 
Safety Endpoints and Analyses .........................................................................................................................................................28 
Poolability ..............................................................................................................................................................................................28 
Handling of Missing Data ....................................................................................................................................................................28 
5. 
Data Management……………………………………………………………………………….. 29 
6. 
Deviations from the Investigational Plan…………………………………………………… 29 
7. 
Device Accountability……………………………………………………………………. 29 
8. 
Ethics……………………………………………………………………………………………… 29 
Trial Conduct.........................................................................................................................................................................................29 
Institutional Review Board Review ....................................................................................................................................................30 
Informed Consent .................................................................................................................................................................................31 
Coverage of Expenses ........................................................................................................................................................................31 
Confidentiality .......................................................................................................................................................................................31 
9. 
Data Handling and Record Keeping…………………………………………………………. 32 
Source Documents ..............................................................................................................................................................................32 

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v 
Data Collection .....................................................................................................................................................................................32 
Record Retention .................................................................................................................................................................................33 
10. 
Quality Control and Quality Assurance……………………………………………………... 33 
Site Training ..........................................................................................................................................................................................33 
Investigator Training ............................................................................................................................................................................33 
11. 
Adverse Events and Serious Adverse Events……………………………………………... 34 
General ..................................................................................................................................................................................................34 
Adverse Event Reporting ....................................................................................................................................................................35 
Definition of an Adverse Event (AE) ..................................................................................................................................................35 
Protocol Specific AE Definition/Collection ..........................................................................................................................................35 
Definition of Serious Adverse Event (SAE) ......................................................................................................................................36 
Causality Assessment of Adverse Events ........................................................................................................................................36 
Adverse Event Severity Assessment ................................................................................................................................................36 
Withdrawal Due to Adverse Events (See Also Section on Subject Withdrawal) .........................................................................37 
Eliciting Adverse Event Information ...................................................................................................................................................37 
Reporting Requirements .....................................................................................................................................................................37 
Serious Adverse Event Reporting Requirements ............................................................................................................................37 
Non-Serious Adverse Event Reporting Requirements ...................................................................................................................38 
Reporting Requirements to Regulatory Authorities .........................................................................................................................38 
12. 
Committees………………………………………………………………………………………. 38 
Data and Safety Monitoring Board.....................................................................................................................................................38 
13. 
Publication Policy……………………………………………………………………………….. 38 
14. 
Bibliography……………………………………………………………………………………… 39 
 
16. 
Appendix 2 – Diabetic Foot Ulcer Scale – Short 
Form………………………………………………………………………… 
42 
 

 
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This document contains information that is confidential and proprietary. The contents of this document may not be copied without written 
permission from the Sponsor. 
 
1 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
Primary Study Contacts 
UT Southwestern Medical Center, Department of Plastic Surgery 
Principal Investigator 
Lawrence A Lavery 
email 
larry.lavery@utsouthwestern.edu 
phone 
214.648.9159 
Parkland Hospital, Department of Plastic Surgery 
Principal Investigator 
Peter Crisologo 
email 
peter.crisologo@utsouthwestern.edu 
phone 
214.648.7284 
 
 

 
STU2020-1386, Lavery, FormA3-ResearchProtocol-v11.08.22, Mod_10, 01-03-23 
 
This document contains information that is confidential and proprietary. The contents of this document may not be copied without written 
permission from the Sponsor. 
 
2 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
Executive Summary 
Title of Study 
Study to Evaluate Celliant Diabetic Medical Socks to Increase Tissue Oxygenation 
and Incidence of Complete Wound Closure in Diabetic Foot Wounds 
Protocol Number 
HGX2020-01 
Study Purpose 
The purpose of this study is to demonstrate that the use of Celliant Socks 
increases tissue oxygenation (via oxygen saturation, StO2) and incidence of 
wound closure in subjects with diabetic foot ulcers. This study will use 
hyperspectral imaging and wound assessment to measure these outcomes.  
Study Design 
This study is a prospective, multicenter, double-blind, 1:1 randomized clinical trial. 
Enrollment 
The study will enroll 254 evaluable subjects total, 127 per arm to meet the Primary 
Endpoint. Enrollment may continue up to twenty-five hundred (2500) evaluable 
subjects total to meet the Key Secondary Endpoint of complete wound closure.  
Investigational 
Sites 
UT Southwestern, Department of Plastic Surgery 
Parkland Hospital, Department of Plastic Surgery 
Study Duration 
Up to 28 weeks (including run-in and followup phase) 
Efficacy Endpoints 
Primary Endpoint: To compare the percent change from baseline in tissue 
oxygenation in Celliant and Control treated groups 12 weeks post initial application, 
as measured by hyperspectral imaging. 
Key Secondary Endpoint: To compare the incidence of complete wound closure 
of Celliant and Control treated groups 12 weeks post initial application. 
Other Secondary Endpoints: 
1. Change in pain assessment as reported using the Visual Analog Scale 
(VAS)  
2. 3-month follow-up to assess wound closure and reoccurrence 
3. Accelerated wound closure as measured by changes in wound area, 
depth and volume. 
4. Assessment of Compliance 
5. Outcomes of Diabetic Foot Ulcer Scale – Short Form 
6. Study related AE/SAEs 
Safety Endpoints 
The incidence of events reported 
Study Groups 
Subjects will be randomized 1:1 to either Active or Control medical sock for 
therapy. All participants will receive standard of care (SOC) for their wound 
therapy. This includes physician choice of selected dressings and offloading 
techniques.  
1. Active Therapy: Celliant Sock  
2. Control Therapy: Control Sock 
 
 
 

 
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3 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
Background and Rationale 
There is a worldwide epidemic of diabetes. Foot ulcers are one of the most common 
complications in diabetic patients leading to amputation and hospitalization [1, 2]. Approximately 
one quarter of all hospital days for persons with diabetes are related to foot complications [1-3]. 
The majority of amputations (50%-83%) are in people with diabetes [4-7]. Foot ulcers are the 
most common underlying cause of amputation. 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 [8, 9]. 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 [10].  
Continuous supply of oxygen to the tissue through microcirculation is vital for the healing process 
and for resistance to infection [11]. Hypoxia of the wound primarily caused by vascular limitations 
is intensified by coincident conditions (e.g. infection, pain, anxiety and hyperthermia) and leads 
to poor healing outcomes [12, 13]. Sufficient oxygenation is especially important for cell 
proliferation, bacterial defense, angiogenesis, collagen synthesis and epithelialization [14]. From 
a diagnostic standpoint, measurements of wound oxygenation (transcutaneous O2 
measurements or TCOM) are commonly used to guide treatment planning such as amputation 
decision [15-20]. In preventive applications, optimizing wound perfusion and providing 
supplemental O2 in the peri-operative period reduces the incidence of post-operative infections 
[21-23]. Hopf et al. [24] conducted a prospective study of 130 surgical patients to determine 
whether subcutaneous wound oxygen tension could predict the development of wound infection. 
Correction of wound pO2 (partial pressure of oxygen in the wound tissue) may, by itself, trigger 
some healing responses [25-33]. More importantly, approaches to correct wound pO2 favorably 
influence outcomes of other therapies such as responsiveness to growth factors and acceptance 
of grafts [25, 34, 35]. 
Infrared (IR) radiation is an electromagnetic spectrum with a wavelength of .70 to 100 μm. It has 
been observed that IR can stimulate cell proliferation, increase tissue regeneration in vitro, and 
increase the topical skin temperature [36-38]. Recent studies have been demonstrated that IR 
has been used for soothing effect and reducing pain of the wound site after standard medical 
wound treatments, even in clinical observations where wounds under exposure to IR decreased 
the wound healing times [39-42]. 
Summary of Findings from Previous Studies 
The biological effects of infrared (IR) radiation (.70-100um) that have been observed in both in 
vitro and in vivo studies have launched IR as a promising modality for certain medical conditions 
(reviewed in [37]). Technological advances have provided new techniques for delivering IR 
radiation to the human body. Specialty lamps and saunas delivering pure mid-radiation (5-25 
um; eliminating completely the near- and far-infrared bands) have become safe, attractive, and 
widely used devices to generate therapeutic effects. Additionally, studies have shown that IR-
emitting apparel technology can also have a physiological effect on athletes during exercise 
[43]. 
For IR used as a therapeutic modality, the alternative terms “biogenetic radiation” and 
“biogenetic rays” have been widely used in the popular literature. IR wavelengths are too long 
to be perceived by the eyes, however, the body experiences its energy as a gentle radiant heat 

 
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4 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
which can penetrate over 1.5 inches (4 cm) beneath the skin [42]. In the IR radiation bands, only 
mid-IR transfers energy purely in the form of heat, which can be perceived by the 
thermoreceptors in human skin as radiant heat [44]. Not only is mid-IR absorbed by the human 
body, but it is also emitted by the body in the form of blackbody radiation (3 to 15 microns, with 
an output peak at 9.4 micron). IR energy is sufficient to increase the energy of rotational and 
vibrational modes of motion in bonds in many biological molecules (including the water 
molecules which predominate in tissue). Resulting epidermal temperature is higher when the 
skin is irradiated with IR than if similar energy densities delivered using shorter wavelengths are 
used. The prolonged erythemal response from IR exposure has been proposed to be due to 
increased epidermal temperatures associated with it, but levels of IR that do not produce any 
detectable skin heating can also have biological effects.  
A possible explanation for these biological effects that occur without any detectable temperature 
change in the tissue is that the IR radiation is selectively absorbed by water molecules that are 
associated with ion channels in the membranes within the cell (both plasma membrane and 
organelle membranes)[42]. Water is by far the most important chromophore in the IR spectral 
range, both because of its high absorption coefficient, and its high abundance (70%) in tissue. 
These water molecules are absorbed on the surface of the so-called “heat-sensitive TRP 
(transient receptor potential) ion channels.” When these “structured” water molecules absorb IR, 
they change their pH by a small but significant amount, which affects the conformation of critical 
amino acids in the protein components of the ion channel. These TRP channels are calcium ion 
channels and an increase in cellular calcium can activate several important signaling pathways 
and even activate transcription factors. One specific TRP channel (TRPV3) has been linked to 
epithelial wound healing [45] through inducing release of nitric oxide (NO) from keratinocytes 
[46, 
47]. 
Another, 
TRPC6, 
has 
been 
linked 
to 
regulate 
fibroblast-myofibroblast 
transdifferentiation and deletion of this protein results in delayed dermal wound healing in 
rodents [48].  
As such, fibers embedded with materials and woven into fabrics are being used as garments, 
bedding and wraps to generate IR radiation, which is converted from the energy supplied by 
body heat, and provide health benefits from its effects. In a similar manner, discs of FIR emitting 
ceramic material have been applied to the human body to produce a beneficial effect. For 
instance, a blanket containing discs has been reported to improve quality of sleep [3] and single 
discs were applied to the breasts of women who encountered difficulty in producing sufficient 
breast milk during lactation [49]. Gloves have been made out of FIR-emitting fabrics and there 
have been reports that these gloves can be used to treat arthritis of the hands and Raynaud’s 
syndrome [50].  
Celliant® Diabetic Medical Socks are intended to increase tissue oxygenation thereby increasing 
blood flow and local circulation leading to improved wound healing outcomes and possible pain 
reduction. Celliant® fibers, yarns and fabrics, like other products described above, are designed 
to re-emit infrared light derived from heat energy generated by the wearer back into the wearer’s 
skin. In 7 preliminary studies (including 3 published), application of the Celliant® Diabetic Medical 
Socks (or other Celliant®-containing systems) results in improved blood flow in healthy and 
diabetic subjects as measured by oxygen availability in skin and superficial tissue by 
transcutaneous partial pressure of oxygen (tcPO2) and reduced pain. A summary of these 
studies follows: 

 
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5 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
Published: 
2019 tcPO2 increased by up to 10% and increase in grip strength of 12%, n=24, Hamblin 
and Gordon (shirts)[51] 
2018 tcPO2 increased by 8.4% after 90 minutes, n=153, Hamblin and Gordon (shirts)[52] 
2009 Reduction in foot pain in diabetic/neuropathic subjects, n=55 Gordan (socks)[53] 
Papers: 
2012 tcPO2 increase of 17% in healthy subjects, n=100, Shaojing (socks)[54] 
2012 tcPO2 increase of 7% in healthy subjects, n=51, Gordon (shirts)[55] 
2005 tcPO2 increase of 12%-24% in healthy subjects, n=13, McClue (gloves and 
socks)[56] 
2003 tcPO2 increase of 12% in hands and 8% in feet of diabetic subjects, n=20 (gloves 
and socks) [57] 
In all of these studies (n=7), measurements obtained while wearing Celliant® -either shirts, socks 
and/or gloves- were compared to measurements obtained while wearing control products 
identical in construction except lacking the center-loaded, thermo-reactive ceramic particles in 
the PET yarn. Furthermore, no significant differences in blood pressure, heart rate, or skin 
temperature were observed in measurements obtained while subjects wore control or Celliant® 
products.  
Device Description 
Celliant® Diabetic Medical Sock 
Celliant® Diabetic Medical Socks (“Celliant Socks”) are intended to provide infrared radiation 
(IR) to increase tissue oxygen thereby increasing blood flow and circulation in the affected area 
leading to an effect on wound closure outcomes and possible pain reduction. Hologenix intends 
to produce Celliant fibers and yarns that are woven or knitted in combination with other 
materials, such as polyester, cotton and wool into hosiery (socks) and wraps or fabrics that are 
then used in garments such as shirts and pants; bed linens such as sheets, pillows and mattress 
pads; and clothing accessories such as sweatbands and shoe liners as well as seat covers, 
home and office furnishings.  
Celliant® fibers are comprised of a proprietary blend of infrared (IR) emitting ceramic materials 
mixed with polyethylene terephthalate (PET). The proprietary blend consists of the following 
components: alumina oxide; silicon dioxide; and titanium dioxide. The Celliant fibers are woven 
or knitted into yarn and used to manufacture the Celliant Sock. The Celliant Sock content will 
be 82% Celliant polyester, 13% Nylon and 5% Spandex. Celliant fibers absorb energy (heat) 
generated by the wearer’s body by radiation, convection and conduction, and also from the 
environment, and re-emit the energy as infrared radiation back into the wearer’s body. Testing 
has shown that fabrics containing Celliant fibers have a higher emissivity (.25 mW/cm2 at 35 
Celsius) in the 2.5–20 µm wavelength range compared to similar PET-only fabrics [58, 59]. 
Moreover, several preliminary studies have shown that the application of Celliant Socks (or 
other Celliant-containing systems) results in improved blood flow in healthy and diabetic 

 
STU2020-1386, Lavery, FormA3-ResearchProtocol-v11.08.22, Mod_10, 01-03-23 
 
This document contains information that is confidential and proprietary. The contents of this document may not be copied without written 
permission from the Sponsor. 
 
6 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
subjects as discussed above. Therefore, it is believed that the increased infrared radiation 
emission from the Celliant garments is associated with this positive physiological impact of 
enhanced blood flow and circulation and increased tissue oxygenation (TcPO2), which may 
have a significant impact in wound healing. 
Control Sock 
The Control Sock will be visually identical to the Active Celliant® Sock. The sock will be made 
of identical materials without the Celliant® components. The Control sock will be 82% standard 
polyester, 13% Nylon, and 5% Spandex. 
Regulatory Status 
Overview 
The Celliant® Diabetic Medical Sock is an investigational device and is not approved in the 
United States to provide infrared radiation (IR) to increase tissue oxygenation or to promote 
complete wound closure by increasing blood flow and circulation or to reduce pain in diabetic 
patients with foot ulcers.  
However, the US FDA has determined the Celliant Products to be medical devices as defined 
in section 201(h) of the Act and are also general wellness products. The Celliant Products are 
medical devices because they are intended to affect the structure or function of the body of man 
by temporarily promoting increased local blood flow at the site of application in healthy 
individuals. 
Proposed Indications for Use 
The Celliant® Diabetic Medical Sock is intended to provide infrared radiation (IR) to increase 
tissue oxygenation (via oxygen saturation, StO2) as measured by hyperspectral imaging (HSI) 
resulting in increased blood flow and local circulation in the affected area which may influence 
wound closure. In a clinical study, adult subjects (22 years and older) with diabetic foot ulcers 
showed an increase in tissue oxygenation and blood flow and local circulation with positive 
wound closure outcomes compared to subjects wearing non-Celliant® Diabetic Medical Socks. 
The Celliant®  Diabetic Medical Sock may also reduce/improve pain 
Benefits and Risks 
Potential Benefits to the Subjects 
There is no promise or guarantee that this product will help heal the subject’s wound, but the 
potential benefit of wearing Celliant® Diabetic Medical Socks is that adults with diabetic foot 
ulcers may experience improved tissue oxygenation and improved wound closure outcomes and 
possible pain reduction compared to adults not wearing Celliant Socks. The clinical results may 
prove this hypothesis. Moreover, the potential benefits may extend beyond the immediate 
closure of chronic foot ulcers. The effects of IR on the tissue of the feet will tend to prevent any 
further lesions or ulcers developing. By increasing the tissue oxygenation, reducing 
inflammation, and stimulating collagen formation in the dermis, the skin may be “strengthened” 
and small traumas which would previously have progressed into a chronic wound may be healed 
up without even being noticed.  

 
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7 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
Additionally, the beneficial effect of Celliant ® Diabetic Medical Socks in wound closure can be 
derived from what is known about photobiomodulation (PBM). PBM involves the use of red light 
(600-700nm) or near-infrared light (760-1070nm) applied periodically to the tissue. By definition 
PBM is delivered using a powered light source such as a laser or a light-emitting diode (LED) 
array. There have been several successful clinical studies using PBM for healing of chronic 
wounds including diabetic foot ulcers. The difference between PBM and Celliant is the 
wavelength and the fact that the IR emitted from a Celliant ® Diabetic Medical Sock is being 
consistently delivered into the feet as long as the socks are worn. 
Potential Risk 
Participation in this clinical investigation presents low risks to subjects. These products have 
passed biocompatibility testing and there are no known risks of wearing Celliant® Diabetic 
Medical Socks. There have never been any reports of allergies developing to the fabric (PET) 
or to the minerals (Al2O3, SiO2, TiO2). Some general risks associated with any new wound 
dressing or skin-contact devices are listed in the table below. 
Risks 
Disorders/Conditions 
Skin and 
Subcutaneous Tissue 
Reaction/Allergy  
 
• 
Skin rash, irritation, blistering  
• 
Pruritus/itching  
• 
Skin excoriation/breakdown  
• 
Skin scarring if significant skin irritation were to occur  
• 
Skin hyper/hypo-pigmentation at and/or around dressing 
application area  
• 
Erythema/redness, edema, inflammation, or swelling at 
and/or around dressing application area 
Mild Pain or Discomfort  
• 
Tenderness/minor ache at and/or around dressing 
application area  
• 
Perspiration associated with wearing sock 
• 
Decreased sleep or sleep quality 
• 
Paresthesia (numbness, tingling, prickling, creeping 
sensation)  
Other  
• 
Risks to privacy 
• 
Loss of data confidentiality 

 
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8 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
Protection Against Risks 
Protected health information (PHI) of subjects in clinical investigations are kept as confidential 
as possible in accordance with the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). However, confidentiality cannot be assured. The table below lists the entities granted 
access to protected health information (PHI). 
Entity 
Reason for Access 
Sponsor’s Clinical 
Representative (Monitor) 
Assess data for accuracy and completeness 
Institutional Review Board 
(IRB) 
Ensure protection of research subjects  
Regulatory Authorities (e.g. 
Food and Drug 
Administration 
Audit clinical trial for Subject protection and data integrity 
Investigator/Site Staff 
Collection and assessment of data for accuracy and 
completeness 
Alternatives to Participation  
Subjects are not required to participate in this research study. As an alternative to study 
participation, subjects will receive wound care treatment per physician discretion. 

 
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permission from the Sponsor. 
 
9 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
1. Trial Objectives 
The objective of this trial is to evaluate percent change from baseline in tissue oxygenation (via 
oxygen saturation, StO2) in Celliant and Control treated groups 12 weeks post initial application, as 
measured by hyperspectral imaging in 254 evaluable patients total when a Celliant® Diabetic Medical 
Sock (n=127) is worn over the patients dressing as compared to wearing a Control Medical Sock 
(n=127). Enrollment may include up to 2500 total subjects to meet the Key Secondary Endpoint. The 
Key Secondary Endpoint is to compare the incidence of complete wound closure of Celliant and 
Control treated groups 12 weeks post initial application*. Other secondary outcomes include wound 
evaluation at 3 months post complete wound closure, accelerated wound closure as measured by 
changes in area, depth and volume as well as treatment compliance and assessment of pain 
reduction.  
*if the study wound is deemed closed on the week 12 visit, the patient will continue using the 
sock and the wound will be evaluated on week 14 to confirm healed state. 
2. Selection and Withdrawal of Subjects 
Inclusion Criteria: 
• 
Diagnosis of diabetes mellitus 
• 
Subject is willing and able to wear a sports-style tube sock at least 22 hours a day. 
• 
Ankle Brachial Index (ABI) ≥0.5 (bedside ABI is acceptable for screening purposes as 
the formal imaging ABI may not be resulted prior to surgery) or toe pressure of ≥30mmHg 
• 
One or more diabetic foot ulcers (only one will be treated) that are located in the ankle 
area or below that has persisted a minimum of 30 days prior to the Screening visit 
• 
Diabetic Foot Ulcers ≥0.5cm2 and ≤16cm2 
• 
Ulcer grade I or II, Stage A, I or II Stage B, according to University of Texas Wound 
Classification System 
• 
22 years of age or older 
Exclusion Criteria: 
• 
Subject has untreated osteomyelitis 
• 
Ulcers within 5cm of target ulcer or connected by fistulas 
• 
Ulcer has decreased by 30% or more at the end of the run-in period 
• 
Subject has active untreated cellulitis 
• 
Subject has active untreated charcot 
• 
Major immunodeficiency including HIV. 
• 
Is pregnant or plans to become pregnant 
• 
Is nursing or actively lactating 

 
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10 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
• 
Developmental disability/significant psychological disorder that in the opinion of the 
investigator could impair the subject’s ability to provide informed consent, participate in 
the study protocol or record study measures, including untreated schizophrenia, bipolar 
disorder and psychiatric hospitalization within the last 2 years. 
• 
Active alcohol or substance abuse in the opinion of the investigator that could impair the 
subject’s ability to provide informed consent, participate in the study protocol or record 
study materials 
 
Withdrawal of Subjects 
Subjects may withdraw from the study at any time at their own request, or they may be withdrawn 
at any time at the discretion of the PI for safety, behavioral, or administrative reasons. If a subject 
does not return for a scheduled visit, every effort should be made to contact the subject, per 
institutional protocol. In any circumstance, every effort should be made to document subject 
outcome. The Investigator should inquire about the reason for withdrawal, request that the 
subject return for a final visit, if applicable, and follow up with the subject regarding any 
unresolved AE's.  
Any related SAE occurring within 14 days following subject discontinuation must be reported to 
Hologenix and be followed up until stabilization or resolution. If the Subject withdraws from the 
study, and also withdraws consent for disclosure of future information, no further study 
evaluations will be performed, and no additional data will be collected. The PI may retain and 
continue to use any data collected before such withdrawal of consent.  
The Investigator may choose to withdraw their own participation or discontinue a Subject from 
study with or without their consent for any of the following:  
• 
Adverse Events 
• 
Non-compliance 
• 
Safety 
• 
Complications 
• 
Unforeseen events 
A patient who experiences the noted changes, relative to previous measures, in the following 
parameters will be terminated early from study participation 
• 
An increase in ulcer size by 50% or more prior to debridement from previous visit. 
• 
An increase in pain rating by 50% or more from previous visit. 
• 
Presence of infection as determined by 2 more bacterial infection indicators that requires 
treatment outside the study scope 
• 
Presence of osteomyelitis that requires treatment outside the study scope. 
• 
Need for wound management outside the study scope 

 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
• 
Or for any reason that may, in the opinion of the Investigator, affect negatively the 
wellbeing of the subject.  
If for any reason the subject is withdrawn from the clinical investigation, the Investigator will 
inform the subject accordingly.  
3. Clinical Investigation Plan 
Description of Trial Design 
This study is designed as a prospective, multi-center, double-blind, 1:1 randomized clinical trial 
to assess the clinical safety and efficacy of Celliant® Diabetic Medical Socks to increase tissue 
oxygenation and complete wound closure. 
Investigational Sites 
University of Texas Southwestern, Department of Plastic Surgery 
PI: Lawrence A. Lavery, DPM, MPH 
Location: Dallas, TX 
Parkland Hospital, Department of Plastic Surgery 
PI: Peter Crisologo, DPM 
Location: Dallas, TX 
 
Duration of Subject Participation 
• 
Screening: Within 7 days Run-In initiation 
• 
Run in Evaluation: 2 weeks of evaluation 
• 
Treatment period: Up to 12 weeks 
• 
Follow-up period: Up to 3 months post wound closure event 
• 
Total duration of subject participation: Up to 28 weeks 
Screening and Enrollment 
Patients who present to the investigator's institution (through clinic admission, direct transfer 
from another facility, or through the emergency room) may be recruited to participate in the 
study. No direct marketing for subject recruitment will be done.  
Patients approached for study participation will be at least 22 years of age at the time of consent, 
will undergo wound assessment, and meet all eligibility requirements. Those meeting eligibility 
criteria for the study will have the study explained to them by the Investigator. An Informed 
Consent Form will be provided to sign according to Section 11 prior to undergoing any study 
procedures. Patients will be encouraged to ask questions of the investigators. It will be made 
clear to the patient that not participating in the study will in no way influence the treatment plan 
or the relationship with the physician.  

 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
Wound Selection 
Only one wound per subject will be included in the study. Subjects with multiple wounds will 
have each wound measured for volume. The wound with the largest volume meeting all eligibility 
requirements will be chosen for inclusion in the study. The etiology of the chosen wound, and if 
it is a new or recurring, will be documented.  
Randomization and Blinding Procedure  
Prior to study initiation, Active and Control samples will be prepared in sealed and labeled as A 
or B, also randomization envelopes will be provided to the research staff and used to obtain 
randomization assignment. Within each randomization envelope, there is an assignment of A or 
B. After run-in evaluation, the subjects wound will be debrided and dressed with SOC. At the 
end of the procedure, subjects who continue to meet all inclusion and no exclusion criteria will 
be randomized in a 1:1 ratio to be treated with either Control or Celliant therapies, stratified by 
wound size (greater than size of 4 cm2) and study center. Study staff will use the randomization 
number labels and sock assignment of socks A or B contained in the envelope. The number will 
become the subject ID. The research staff will note the randomization number and the treatment 
assignment letter (A or B) on the CRF. The key, indicating therapy assignments (Active or 
Control), will only be available to staff not directly involved in the study until after the subject has 
completed study activities. 
 
Visit Schedule 
Study procedures for each phase of study are outlined below. In a later section, details on each 
study procedure are described, including equipment designation. 
Screening  
1. Explain purpose and nature of the study and obtain signature on the informed consent 
document. 
2. Screen the subject against protocol inclusion and exclusion criteria, including all 
pertinent tests. 
a. ABI and/toe pressure 
b. Ulcer History, measurement, and classification 
c. Urine Pregnancy test (if indicated) 
Baseline (may be done as same day as screening procedures) 
1. Obtain general medical history and demographic information and social history 
2. Complete a physical examination, body weight, height, and vital signs, including 
measurement of resting heart rate, respiratory rate, and blood pressure while seated. 
3. Select the target ulcer 
4. Obtain complete history pertinent to DFU disease including duration of the target ulcer, 

 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
previous and current treatment. 
5. Perform debridement if indicated. Debridement is to be performed using curette, 
scissors, scalpel, or forceps. 
6. Collect 4 tissue specimens. Two in RNA later and two in DNA/RNA shield. 
7. Perform standardized photography and measurement of the study wound (eKare or 
available camera with ruler). Assess the post-debridement ulcer area (cm2), perimeter 
(cm), and greatest depth (cm) using the inSight device (eKare, Fairfax, VA). These 
values are the baseline measurements for assessing accelerated wound closure at the 
two-week run-in visit. 
8. Perform baseline SPP (note – this procedure can be performed at any visit from baseline 
up to therapy initiation but before therapy is started). 
9. Perform baseline tcpO2 (note – this procedure does not need to be performed at baseline 
visit and can be performed at any visit through Run-In week 2/Therapy initiation visit). 
10. Perform baseline hyperspectral imaging assessment on the dorsal and plantar aspects 
of the foot. 
11. Perform neuropathy and pain assessment. 
12. Obtain results from SOC hematology, blood chemistry, etc. that were not covered in 
inclusion/exclusion studies. 
13. Subjects who do not meet eligibility and fail to qualify to enter the Run-in will be deemed 
Screen failures and discharged, noting the reasons for disqualification. 
14. Collect all relevant concomitant medication (antibiotics, antifungals and other anti-
infective therapies) 
15. Wounds will be dressed SOC and offloaded per physician discretion. 
16. Subjects who qualify to enter the run-in will be instructed to refrain from using excluded 
medications and return to the office for Run-in Visit 2 within 7 (±4) days.  
Run-In Procedures/Therapy Initiation 
Week 1 Run-in: 
1. Assess target ulcer. 
2. Perform debridement if indicated. Debridement is to be performed using a curette, 
scissors, scalpel, or forceps. 
3. Perform standardized photography of the study wound. 
4. Assess the post-debridement ulcer area (cm2), perimeter (cm), and greatest depth (cm) 
using the inSight device. 
5. If wound size (ulcer area) increases/decreases by 30% or more, patient will be deemed 
a screen failure and removed from the study. 
6. If wound size (ulcer area) decreases by less than 30%, patient wound will be treated with 
standard of care and return for run-in Week 2 Run-In within 7 (±4) days. 

 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
7. Perform hyperspectral imaging assessment on the dorsal and plantar aspects of the foot. 
8. Perform pain assessment. 
9. Collect all relevant concomitant medication (antibiotics, antifungals and other anti-
infective therapies) 
10. Wounds will be dressed SOC and offloaded per physician discretion. 
Week 2 Run-in/Therapy Initiation: 
1. Assess target ulcer 
2. Perform debridement if indicated. Debridement is to be performed using curette, 
scissors, scalpel, or forceps. 
3. Perform standardized photography of the study wound. 
4. Assess the post-debridement ulcer area (cm2), perimeter (cm), and greatest depth (cm) 
using the inSight device. 
5. If wound size (ulcer area) increases/decreases by 30% or more, patient will be deemed 
a screen failure and removed from the study. 
6. If wound size (ulcer area) increases/decreases by less than 30%, patient wound will 
enter the study and randomized to either the Celliant Active or Control treatment arm. 
7. Perform hyperspectral imaging of the dorsal and plantar aspects of the foot 
8. Perform pain assessment. 
9. Collect all relevant concomitant medication 
10. Wound will be dressed with SOC and either Celliant Active or Control Sock applied. 
11. Wound will be offloaded. 
12. Provide subject with any additional medical socks needed until the next visit. Instruct the 
subject to change the socks if they become wet, soiled, or bloody and under any 
conditions dictated by PI instructions.  
Therapy/Treatment Phase 
Study Visit 1-11: 
1. Document study compliance information from the subject 
a. Amount of time the sock was worn throughout the week 
b. Was it worn during the day/night? 
c. When/why the sock was changed. 
d. Has the sock been on in the 3 hours leading up to the appointment? 
2. Remove sock and dressing and immediately perform hyperspectral imaging of the dorsal 
and plantar aspects of the foot if wound is active or closed. 
3. Assess target ulcer (if wound has closed, document as such, perform steps 7 and 8 and 

 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
skip to Study Visit – Wound Closed). 
4. Debridement is to be performed, if indicated, using curette, scissors, scalpel, or forceps. 
If debridement is necessary at weekly visits, all therapy must be removed and replaced 
post-debridement. 
5. Collect 4 tissue specimens at week 3 and at week 6. Two in RNA later and two in 
DNA/RNA shield. 
6. Perform standardized photography of the study wound. 
7. Assess the ulcer area (cm2), perimeter (cm), and greatest depth (cm) using the inSight 
device - if the wound is deemed closed by the physician, skip to EOS visit.   
8. Perform SPP and tcPO2 measurements at Visit 4 (maybe be taken instead at visit 5 or 
6 if subject has not been wearing their treatment sock leading up to the visit or misses 
this visit). 
9. Collect all relevant concomitant medication 
10. Perform pain assessment. 
11. Redress the wound with standard of care (if wound is still active) and apply Celliant 
Active or Control Sock and apply offloading (if indicated). 
12. Wound will be offloaded. 
13. Provide subject with any additional medical socks needed until the next visit. Instruct the 
subject to change the socks if they become wet, soiled, or bloody and under any 
conditions dictated by PI instructions. Instruct the subject that they must wear the sock 
at all times and that including the 3 hours leading up to the next study visit.  
Study Visit - Wound Closed 
1. The study wound is defined as closed when there is complete skin re-epithelialization 
without drainage or dressing requirements confirmed by the evaluating physician at 2 
consecutive study visits 2 weeks apart. 
2. At this visit the subject will perform the EOS evaluation and enter the follow-up phase of 
the study.  
Study Visit 12/EOS 
1. If the study wound closes prior to the 12-week study mark, subjects will perform EOS 
visit at the time of wound closure. See Study Visit - Wound Closed. 
2. A subject whose wound does not close completely by week 12 will exited from the study 
after the week 12 wound evaluation. 
3. Document study compliance information from the subject 
a. Amount of time the sock was worn throughout the week 
b. Was it worn during the day/night? 
c. When/why the sock was changed. 

 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
d. Has the sock been on in the 3 hours leading up to the appointment? 
4. Remove sock and dressing and immediately perform hyperspectral imaging of the dorsal 
and plantar aspects of the foot if wound is active or closed. 
5. Assess target ulcer (if wound has closed, document as such, perform steps 7-12 and 
skip to Study Visit – Wound Closed). 
6. If the subject still has a large enough wound, collect 4 tissue samples. Two in RNA later 
and two in DNA/RNA shield. 
7. Perform standardized photography of the study wound. 
8. Assess the ulcer area (cm2), perimeter (cm), and greatest depth (cm) using the inSight 
device.  
9. Perform SPP if wound is active or closed. 
10. Perform tcpO2 if wound is active or closed. 
11. Perform pain assessment 
12. Ask the subject if they thought they were in the active or control group 
13. Administer DFS-SF  
14. Collect all relevant concomitant medication 
15. Redress the wound per physician-directed standard of care. 
Study Visit Follow up 
1. If the subject’s wound closes within the 12-week treatment window, they will enter the 
follow up phase of the study. 
2. At 3 months post closure, wound evaluation will be performed as outlined below. This 
follow-up visit will be in person. In the event that an in-person visit is not possible, a 
telehealth visit may be performed and documented as such. 
a. Assess the study wound to determine that it remained closed 
b. If the study wound has reoccurred 
i. record the date of reoccurrence 
ii. measure the size of dehiscence or re-ulceration 
iii. exit the subject from the follow up phase 
c. Assess the study foot for new sites of ulceration 
i. record the date of reoccurrence 
ii. measure the size of dehiscence or re-ulceration 
iii. exit the subject from the follow up phase 
Detailed Study Operations 
Medical Status/History 

 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #:  HGX2020-01 
 
 
• 
The New York Heart Association (NYHA) Functional Classification System: This system 
will be used to classify stage of heart failure. The New York Heart Association (NYHA) 
functional classification system is used to classify the stage of heart failure from Class I 
to IV (as shown in the table below). This system relates symptoms to everyday activities 
and the patient's quality of life. 
Class 
Patient Symptoms 
Class I (Mild) 
No limitation of physical activity. Ordinary physical 
activity does not cause undue fatigue, palpitation, or 
dyspnea (shortness of breath). 
Class II (Mild) 
Slight limitation of physical activity. Comfortable at rest, 
but ordinary physical activity results in fatigue, 
palpitation, or dyspnea. 
Class III 
(Moderate) 
Marked limitation of physical activity. Comfortable at 
rest, but less than ordinary activity causes fatigue, 
palpitation, or dyspnea. 
Class IV (Severe 
Unable to carry out any physical activity without 
discomfort. Symptoms of cardiac insufficiency at rest. If 
any physical activity is undertaken, discomfort is 
increased. 
• 
Body Mass Index (BMI): BMI is calculated as the ratio of body weight in kilograms (kg) 
to height in meters squared (m²).  
• 
Medical History: The following information will be collected from each subject 
• 
previous ulcer history 
• 
amputation history 
• 
lower extremity bypass 
• 
lower extremity angioplasty 
• 
coronary 
artery 
bypass 
surgery 
• 
cardiac angioplasty 
• 
arthritis 
• 
liver disease 
• 
osteoporosis 
• 
malignancy 
• 
bone tumors 
• 
skin pathology 
• 
vital signs (weight, height, 
HR, BP) 
• 
diabetes history 
o duration 
o type 
o medication 
• 
date and type of surgery 
• 
vascular status 
• 
neuropathy
Clinical Lab Values 
• 
BUN (blood urea nitrogen) 
• 
Creatinine 
• 
Estimated GFR (glomular 
filtration rate) 
• 
Hemoglobin A1c 
• 
Blood Glucose 
• 
Prealbumin (transthyretin) 
• 
Albumin 
• 
CRP (C-reactive protein) 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
• 
ESR (Erythrocyte 
Sedimentation Rate) 
• 
White blood cell count 
• 
RBC 
• 
Platelet Count 
• 
Hemoglobin 
• 
Hematocrit 
• 
RDW 
• 
Pregnancy test if subject is 
child bearing potential 
Concomitant Medications 
All antibiotics, antifungals and other anti-infective therapies engaged in by the subject will 
be recorded at screening visits and follow up visits 
Social Factors 
The following social factors will be recorded: 
• 
marital status 
• 
years of education 
• 
occupation 
• 
tobacco use history: number of years of smoking, current or previous smoker, use of 
chewing tobacco, average daily number of cigarettes for current smokers 
• 
alcohol and drug use history: current and/or previous history, types of alcohol/drugs 
consumed in the past and/or present; frequency and amount of alcohol/drugs 
consumed in the past and/or present 
Demographic Variables 
The following demographics will be recorded for each subject:  
• 
Gender: male or female. 
• 
Age 
• 
Language Spoken: English, Spanish, English and Spanish, other(specify) 
• 
Race: Caucasian, African American, American Indian, Asian/Pacific Islander. 
• 
Ethnicity: Hispanic or not 
Wound History and Assessment 
• 
Wound History and Evaluation: We will use the University of Texas Ulcer Classification 
to document ulcer severity. Our group developed and validated this classification system. 
We will enroll subjects with UT ulcer classification IA, IIA, IB, and IIB ulcers. These are 
ulcers without penetration to tendon, capsule or bone and without PAD. This 
classification system is a 4 x 4 matrix that includes the depth of the ulcer or the ulcer 
Grade: (0) pre/post-ulcerative site, (1) full thickness, (2) extends to tendon or capsule, 
(3) extends to bone and the Stage of the ulcer that identifies if there is infection and/or 
PAD: (A.) No PAD or infection, (B.) infection, (C.) PAD (D.) infection and PAD.  

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
 
 
 
 
 
 
• 
Wound Measurements and Debridement: Debridement will be performed per physician 
discretion using a scalpel or bone curette to remove all surrounding callus, wound debris, 
necrotic tissue, fibrin, eschar and non-viable tissue to create a bleeding wound bed. We 
will objectively measure ulcer debridement and changes in wound size using changes in 
wound volume and area from wound measurements with the inSight digital 3D 
measurement device (eKare, Fairfax, VA). Digital photos will be taken after debridement. 
We will take post-debridement measurements of wound volume and area. Gardner et al 
reported that volume measurements with a digital image evaluation system was reliable. 
• 
Safety Measures: Each of the following measures will be rated on the following 5-point 
Likert scale, as well as a descriptive evaluation being recorded, as applicable, for the 
study wound: 1) absence or 2) presence of the following: 
• 
Erythema 
• 
Discharge/drainage 
• 
Malodor 
• 
Tissue necrosis 
Vascular Assessment 
We will assess perfusion/tissue oxygenation with three approaches; ABI (bedside may be 
done for screening if formal ABIs have not yet been performed/resulted), Skin Perfusion 
Pressure, and Hyperspectral Imaging. We will evaluate Skin Perfusion Pressure (SPP) and 
Transcutaneous Oxygen (tcpO2) measurements using the 510(k) cleared PeriFlux 6000 
Combined system, K131253 (Perimed Inc, Las Vegas, NV) on the dorsal and plantar 
angiosomes of the affected foot and obtain toe pressures and waveforms. Hyperspectral 
imaging using the 510(k)-cleared Kent SnapshotNIR Camera, K113507 (Calgary, AB, 
Canada) will be performed to evaluate the periwound tissue surrounding the ulcer and the 
angiosomes on the dorsal and plantar aspects of the foot.  
Neurological Assessment 
Semmes-Weinstein monofilament evaluation will be performed. We will assess light touch 
and pressure sensation at five sites on the study foot using a 10-gram monofilaments. We 
will perform Vibration Perception Threshold (VPT); a device that uses vibration to test how 
well your feet can detect gentle pressure. 
 
Degree of Pain Rating 
The subject will record his or her current degree/level of pain for the study wound using the 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
following 10cm (100mm) long Visual Analog Scale (VAS) labeled from ‘0’: no pain to ‘10’: 
worst pain imaginable 
No pain 0____________________________________________10 Worst Pain Imaginable 
The VAS is the most commonly used scale for assessing pain [60]. The VAS is a simple 
scale that consists of a 10cm line anchored at one end by a label that indicates total absence 
of the measure being evaluated and at the other end by a label that indicates the worse 
imaginable presence of the measure being evaluated. The subject marks on the line the spot 
for the intensity of the measure, which is then measured using a ruler (in mm units).  
Infection Evaluation 
The following clinical indicators of significant bacterial infection will be recorded as present 
or absent for the study wound. ‘Significant Bacterial Infection Clinical Indicators’ are defined 
in this study as those presenting as excessive beyond which would typically be expected 
given the clinical condition and nature of the wound type.  
• 
local heat 
• 
spreading redness 
• 
swelling 
• 
increased purulent exudate (draining pus) 
• 
odor 
• 
cellulitis 
• 
loss of function 
• 
fevers  
• 
chills 
Sock Use Instructions 
The subjects will be provided with 10 pairs of socks on the initial visit and instructed that the 
socks may be washed as normal laundry as needed (bleach or no bleach). Subjects will be 
supplied additional pairs as needed on a case by case basis. The sock change frequency 
will be dictated by the physician; however, the subject will be instructed to change the sock 
as with any other sock if it becomes wet, soiled, or bloody.  
Patient Reported Outcomes 
The Diabetic Foot Ulcer Scale – Short Form (DFS-SF) (Appendix B) will be used to collect 
patient reported outcomes in this trial. The DFS questionnaire is designed to assess the 
impact of foot ulcers and their treatment on quality of life in people with diabetes.  
Excluded Medications/Treatments 
During the study procedures, the study subjects will refrain from using hyperbaric oxygen 
therapy (HBOT) and any cellular or tissue-based products (RegranX etc). 
Standard of Care 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
• 
All study wounds will be debrided per physician discretion and documented.  
• 
Wound Dressing:  Two wound care treatments will be available, depending on wound 
status and physician discretion 
o IODOSORB Gel is a sterile antimicrobial dressing formulation of Cadexomer 
Iodine. When applied to the wound, IODOSORB absorbs fluids, removing 
exudate, slough and debris and forming a gel over the wound surface. As the 
gel absorbs exudate, iodine is released, killing bacteria and changing color as 
the iodine is used up. https://www.smith-
nephew.com/professional/products/advanced-wound-management/iodosorb--
iodoflex/iodosorb-gel/ 
 
o Hydrofera Blue READY Foam Dressing protects wounds against infection 
with broad-spectrum antibacterial properties and helps with healing and 
managing chronic, acute and traumatic wounds. This ready-to-use, non-
cytotoxic dressing assists with managing moisture, creating an ideal healing 
environment that does not draw out the process and helps control exudate. 
https://hydrofera.com 
 
o AQUACEL EXTRA Hydrofiber Dressing is composed of two layers of 
Hydrofiber technology stitched together. Specifically suited to help manage 
moderate to highly exuding wounds. https://www.convatec.com/products/pc-
wound-leg-ulcers/aquacel-extra-hydrofiber-dressing 
• 
Offloading:  All subjects who can be offloaded will wear the DH OffLoading Walker. This 
is a removable offloading boot that reduces shear force by stabilizing the foot and ankle 
at 
90°. 
https://www.ossur.com/injury-solutions/products/foot-and-ankle/walkers/dh-
offloading-walker. If patients cannot be offloaded as defined above, a method of 
offloading will be used and documented, both type and reason why the Walker was not 
used.  
 
 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
Delegation of Responsibilities 
Task 
Responsibility 
PI 
Nurse 
CRC 
Determine eligibility of subjects 
X 
 
 
Obtain informed consent 
X 
X 
X 
Randomization 
X 
X 
X 
Medical history 
X 
X 
X 
Dressing removal 
X 
X 
X 
Wound assessment of infection and closure 
X 
 
 
Tissue Collection 
X 
X 
X 
Wound measurements 
X 
X 
X 
Study withdrawal assessment 
X 
 
 
VPT 
X 
X 
X 
10-gram monofilament test 
X 
X 
X 
Hyperspectral imaging 
X 
X 
X 
Skin perfusion pressure measurements 
X 
X 
X 
Transcutaneous Oxygen measurements 
X 
X 
X 
Pain assessment 
X 
X 
X 
Concomitant medications 
X 
X 
X 
Subject compliance assessment and review 
X 
X 
X 
Administer patient reported outcomes  
X 
X 
X 
Dressing Application 
X 
 
 
Study Device Application 
X 
X 
X 
Offloading  
X 
 
 
CRF completion/corrections 
X 
X 
X 
CRF/eCRF signature 
X 
 
 
SAE/AE assessments 
X 
 
 
Update and maintain study documents 
X 
X 
X 
SAE reporting and data clarifications 
X 
X 
X 
 
 
 
 
 
 
 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
Schedule of Events Table 
The table below shows the schedule of planned events for each subject in this study. 
 
Weekly Visits (±4 days) 
 
SC 
BL/-2 
-1 
BL/0 
1-11 
*EOS 
FUP 
@3mo 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
Randomization 
 
 
 
X 
 
 
 
Medical History, Social, 
Demographics, PE, Vitals 
 
X 
 
 
 
 
 
Lab Values 
 
X 
 
 
 
 
 
Vascular - SPP 
 
X 
 
 
X** 
X 
 
Vascular – tcpO2  
 
X 
 
 
X** 
X 
 
Vascular - HSI 
 
X 
X 
X 
X 
X 
 
Monofilament, VPT 
 
X 
 
 
 
 
 
Wound Assessment, Debridement 
 
X 
X 
X 
X 
X 
X 
Tissue Collection (4 pieces)# 
 
X 
 
 
X## 
X 
 
Wound Photography and 
Measurements 
 
X 
X 
X 
X 
X 
X 
Pain Assessment 
 
X 
 
X 
X 
X 
 
Sock Application 
 
 
 
X 
X 
 
 
Offloading 
 
 
 
X 
X 
 
 
Adverse Events 
 
 
X 
X 
X 
X 
X 
Concomitant Medication 
 
X 
X 
X 
X 
X 
 
DFS-SF 
 
 
 
 
 
X 
 
Subject Stipend 
 
 
X 
X 
X 
X 
X 
*if subject is deemed closed at week 12, subject will be observed at week 14 and will enter FUP 
phase 
**Visit 4 only, 5 or 6 if visit 4 is missed 
# Two for RNA later and two for DNA/RNA shield 
## Weeks 3 and 6 
 
Trial Monitoring 
Monitoring visits will be conducted by representatives of Hologenix according to the U.S. CFR 
Title 21 Parts 50, 56, and 812 and ICH Guidelines for GCP (E6). By signing this protocol, the 
Investigator grants permission to the Hologenix contact and appropriate regulatory authorities 
to conduct on-site monitoring and/or auditing of all appropriate study documentation. 
Clinical monitors, qualified by training and experience, will be responsible for monitoring and 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
overseeing the conduct of this study. The clinical monitor will evaluate compliance with the 
protocol, FDA regulations, any specific recommendations made by the investigational site’s IRB 
and the signed Investigator Agreement. Telephone, e-mail and fax communications, as well as 
on-site visits, will be conducted to ensure that this protocol is being followed and that any 
protocol deviations are properly documented. Clinical monitoring will include verification that the 
Informed Consent forms were properly completed for all subjects enrolled in this study, a review 
of clinical records for accuracy and completeness, resolution of missing or inconsistent results, 
reporting of complications, adverse events and unanticipated adverse device effects, and a 
review of source documents. The clinical monitor will verify that the Case Report Forms (CRFs) 
are in agreement with the source documentation and other study-related records available at 
the site. For record verification purposes, the clinical monitor will be provided access to relevant 
hospital records, original laboratory data, and other records and data as they relate to this study 
and as agreed to with the investigator prior to the initiation of the study. The investigator will 
make available to the clinical monitor for review all signed Informed Consent forms, all 
completed CRFs, source documentation and other relevant records for all subjects enrolled at 
the site. It is important that the investigator and other relevant site personnel are available for 
consultation with the clinical monitor during the monitoring visits and that sufficient time is 
devoted at the site for the monitoring process. Additionally, telephone, e-mail and fax 
communications will be conducted on a regular basis with the investigator and the site staff to 
ensure that the protocol is being followed and to address any issues that may occur during the 
course of the study. If a deficiency is noted during an on-site visit (or at any other time during 
the course of the study), the clinical monitor is required to discuss the situation with the 
investigator and the Sponsor (if required) to secure compliance. 
Audits and Inspections 
Internal audits are done periodically to assure regulations, guidelines and protocols are adhered 
to appropriately. Patient binders are reviewed for proper informed consent process 
documentation, case report forms are compared to the source documents and reviewed for 
accuracy and an independent review of the inclusion and exclusion criteria using a checklist. 
Additionally, the use of an auditing and monitoring tool which includes sections on consent, 
HIPAA, on study/treatment, off treatment/off study and a general section. Weekly meetings 
occur to go over each study. If there are any issues that arise, they are brought up and discussed 
at the meeting. 
4. Statistical Analyses 
General Statistical Considerations 
This study is a prospective, sham-controlled, subject and evaluator blinded, 1:1 randomized, 
multicenter clinical study. The duration of the study is up to four months for randomized subjects. 
Sample size may not be reduced less than the expected total enrollment of 254 evaluable 
subjects total but may increase up to a total of 2500 evaluable subjects. Sample size will 
increase based on actual attrition that is expected to be between 5 and 15%. 
The purpose of this study is to evaluate safety and efficacy outcomes related to the Celliant 
Sock (CS). The p-value thresholds for determining statistical significance are 0.05 and 0.025 for 
2- and 1-sided tests, respectively, unless otherwise specified. 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
Data will be presented using summary statistics. For example, continuous data may be 
displayed with the mean, median, minimum, maximum, and/or standard deviation, while 
categorical data may be displayed as proportions and counts. 
Any changes to the analysis of the trial data will be documented either in a future protocol 
amendment or in the SAP.  
Randomization 
Randomization will be conducted in a 1:1 ratio of the Treatment Group (Celliant Sock, n=127) 
or to a sham Control Group (placebo sock, n=127). Randomization will be performed within 
randomly selected block sizes of 3 and 6 with equal probability of group assignment stratified by 
study center and wound size (greater than size of 4 cm2).  
A Sponsor-designated independent statistical consultant will provide the randomization list. 
Sponsor personnel directly involved in the management, conduct, and reporting of the study will 
not have access to randomization assignments until the study is completed.  
Analysis Population 
The primary population for the effectiveness analyses will be the intent-to-treat (ITT) population, 
which will include all randomized subjects regardless of whether the socks were ever worn. 
Subjects will be assessed to the group to which they were randomized, regardless of whether 
they were provided the wrong socks. 
A secondary population for effectiveness analyses will be the (AT) population, including subjects 
that attempted to put on the sock for any amount of time. These subjects will be analyzed 
according to the type of socks (Celliant or Placebo) they received. This population is also the 
safety population, which is the population used for all safety analyses. 
A third population is the modified full analysis set (mFAS), which consists of all subjects that 
report wearing the sock as directed for at least 10 days.  
Sample Size Justification 
Assuming a 2-sided alpha at 0.05, and a power of 0.85, the true mean difference at 12 weeks 
between groups in percent change in tissue oxygenation as measured by hyperspectral imaging 
is estimated to be 8.2 with a standard deviation of 21.7. At a 1:1 allocation of experimental to 
control subjects, a total of 254 evaluable subjects are required. The sample size will increase to 
account for attrition at Week 12.  
Analyzing the sample size for the key secondary endpoint of incidence of complete wound 
closure suggests a much large trial is need. Specifically, at 2500 evaluable total subjects, there 
would be approximately a power of 0.85 to detect a difference in incidence of complete wound 
closure at 12 weeks if the expected incidence of complete wound closure was 25% in the 
experimental group, and 20% in the control group, an absolute difference of 5% between the 
experimental group and the control group. 
Primary Efficacy Analyses 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
The primary efficacy endpoint is an inferential test of whether the Treatment Group (Celliant® 
Diabetic Medical Sock) percent change in tissue oxygenation (via oxygen saturation, StO2) 
compared to the Control Group (placebo sock) at 12 weeks is superior.  
Effectiveness variables will be analyzed relative to the mean of the Weekly visit 0 and -1 tissue 
oxygenation measurements. For purposes of statistical analysis, this mean will be referred to as 
the baseline. 
The hypotheses are: 
H0: %ChgPerfCelliant ≤ %ChgPerfPlacebo 
Ha: %ChgPerfCelliant > %ChgPerfPlacebo 
A mixed model repeated measures (MMRM) will be utilized to model percent changes in tissue 
oxygenation by visit through 12 weeks from baseline to provide the contrast statement at 12 
weeks between groups. Included in the model will be treatment group, the stratification variables 
of wound size (as a continuous variable) and study site. Success on this endpoint requires that 
the 12-week treatment group contrast difference is α<0.025. There is no interim analysis for the 
primary endpoint. The primary endpoint is based on a fixed study design. Regulatory activities 
for all but the key secondary endpoint will begin if this primary endpoint is met. 
Interim Analysis for the Key Secondary Endpoint 
The key secondary endpoint will only be tested for significance if the success criterion for the 
primary endpoint are met at the time of the primary endpoint analysis in 254 evaluable subjects, 
which is the interim analysis for the key secondary endpoint.  
The key secondary endpoint is an inferential test of whether the Treatment Group (Celliant sock) 
incidence of complete wound closure rate (CWCR) compared to the Control Group (placebo 
sock) at 12 weeks is superior.  
The hypotheses for this endpoint are: 
H0: CWCR Celliant ≤ CWCR Placebo 
Ha: CWCR Celliant > CWCR Placebo 
The key secondary endpoint of incidence of complete wound closure at 12 weeks will be blinded 
except to the unblinded Interim Analysis Committee (IAC) until the final analysis for this endpoint 
is conducted. Since the estimated sample size for the key secondary endpoint is anticipated to 
be many times larger than for the primary endpoint and there is some uncertainty relative to the 
anticipated treatment effect, the hierarchical design allowing for the testing of the key secondary 
endpoint, and then the use of the adaptive group sequential design to allow for the potential of 
sample size re-estimation is required for efficiency. 
The IAC is comprised of an unblinded statistician and a subject area medical expert whose sole 
responsibility is to analyze the key secondary endpoint at 254 evaluable subjects to determine, 
according to the Lan-Demets O-Brien Fleming alpha spending function, tested at half of the trial 
information: 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
1) The criterion of early stopping for efficacy for CWCR is met at half of the trial information,  
2) The trial will continue to the preplanned 508 planned evaluable subjects for assessing 
CWCR, based on the conditional power at the interim to be Cp≥ 0.85, 
3) If neither of the first two criteria are met, then sample size re-estimation according to 
the inverse normal method (Lehmacher and Wassmer, 1999) will be conducted to allow 
for a sample size of up to 2500 evaluable subjects total for the study.  
a. The trial will be stopped for futility of the key secondary endpoint if the Cp 
assuming a maximum sample size of 1250 subjects for the study provides a 
CP<0.7. 
b. The trial will have a sample size increase as calculated by the inverse normal 
method to maintain a Cp=0.85.  
With the exception of meeting criterion 1 or 3a, i.e. stopping further enrollment, the results of the 
interim analysis will not be shared with the clinical operations team involved directly in the study 
data at the patient or data management. This communication firewall is required to maintain the 
validity of the secondary endpoint in that subjects before and after the interim analysis are 
handled no differently in a way that would alter the estimated treatment effect. 
A logistic model will be used to control for the stratification variables and assess for the treatment 
effect. Once again, as in the primary endpoint, the baseline wound size will be assessed as a 
continuous endpoint, although the stratification variable is dichotomous. 
Type 1 error is controlled because of the hierarchical testing strategy of the primary endpoint 
and then key secondary endpoints, both at α1-sided=0.025. 
An Interim Analysis Charter (IAC) will be provided solely to provide a communication plan and 
numerical example with SAS code to detail the calculations involved for the key secondary 
endpoint.  
Hierarchical Testing of the VAS Pain Endpoint 
The VAS pain endpoint will be tested as the third hierarchical endpoint, i.e., following testing of 
the primary endpoint and then the total wound closure endpoint. In order for the VAS pain 
endpoint to be tested, the primary endpoint and the TWCR endpoints would both need to be 
statistically significant. The final total sample size as determined by the sample size re-
estimation for TWCR will be applied to the VAS pain endpoint without further modification. 
Evaluability of Data 
Prior to the database lock for the final primary endpoint analysis at 254 evaluable subjects, 
and again at any subsequent lock as dictated by the adaptive design for subjects evaluated 
after the final primary lock, an evaluability meeting will be held. The goal of the evaluability 
meeting is to identify the disposition of study subjects with respect to the predefined study 
populations.  

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
Subject Demographic and Baseline Characteristics 
Demographic and baseline characteristics of enrolled subjects will be summarized. The factors 
will include (but are not limited to): Age, sex, race, BMI (kg/m2), baseline Diabetic and Foot 
Ulcer Scale-Short Form (DFS-SF). Medical history, PE, and vitals will be provided in a listing. 
Additional Efficacy Analyses including Subgroup Analyses 
Secondary Endpoints: To compare the incidence of the below between Celliant and Control 
treated groups: 
1. For subjects whose wound closes within the 12-week period, wound evaluation at 3 
months following complete wound closes for the following parameters 
a. Incidence of wound dehiscence/reoccurrence 
b. Size of reoccurrence 
2. Accelerated wound closure as measured by changes in wound area, depth and volume. 
3. Assessment of Compliance 
4. Change in pain assessment as reported using VAS pain scale 
5. Outcomes of Patient Reported Outcomes 
6. Study related AE/SAEs 
Additional, ad hoc exploratory analyses may also be conducted for efficacy endpoints. 
Safety Endpoints and Analyses 
An overview of events, to include total numbers of events, and total number of subjects will be 
tabulated and presented for all AEs, SAEs, procedure-related AEs by treatment type. Device 
specific risks such as “skin and subcutaneous tissue reaction/allergy” and “mild pain or 
discomfort” will also be tabulated in a separate summary table.  
Additional, ad hoc exploratory analyses may also be conducted for safety endpoints.  
Poolability 
Pooling of outcome data from different clinical study sites will be performed by evaluating the 
homogeneity of the primary efficacy endpoint across sites. If the treatment by site interaction is 
p ≥ 0.2, then homogeneity will be considered to be demonstrated across sites. If p<0.2, then 
site level variable will remain in the analysis models.  
Handling of Missing Data 
A list of subjects who were withdrawn from the study and their associated reasons for withdrawal 
will be provided. A list of subjects lost to follow-up will also be provided. If the missingness of 
tissue oxygenation data or total wound closure data at 12 weeks is missing in more than 7.5% 
of subjects, multiple imputation will be performed, creating n=5 fully imputed complete datasets 
for the primary and key secondary endpoint, to be evaluated combined through a t-test, after the 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
predefined analyses are provided for each imputed data set. A non-imputed analysis will also 
be provided. 
5. Data Management 
Standardized CRFs will be created at all participating sites. Investigators are responsible for the 
accurate completion and timely submission of the data collected during the trial. All data from the 
trial will be entered from the CRFs into a central database. Incoming data will be frequently reviewed 
to identify inconsistent or missing data and any adverse events. Any data issues are to be promptly 
addressed with the investigator Quality assurance procedures will be established to ensure that 
complete, accurate and timely data are submitted, that protocol requirements are followed, and that 
complications, adverse events and adverse device effects are correctly reported and investigated, 
as appropriate. Investigators are to maintain all source documents as required by the protocol, 
including laboratory results, supporting medical records, and signed Informed Consent Forms. The 
source documents will be used during the regular monitoring visits to verify information from the 
database against data contained on the completed CRFs. 
6. Deviations from the Investigational Plan 
Any deviations from the study protocol will be documented as Protocol Deviations in the Source 
Documentation.  
7. Device Accountability 
The Sponsor will ship investigational devices only to the designated investigators participating in this 
study. The Sponsor will not ship investigational devices to any site until evidence of IRB approval 
has been provided to the Sponsor. All investigators are responsible for providing a secure storage 
location for the investigational devices, supervising device use, as well as the disposal and/or return 
of the devices as instructed by the Sponsor. In addition, all investigators shall maintain records to 
document the receipt, use and disposition of all investigational devices received by their site. The 
Sponsor will maintain records of all shipments and disposition of the investigational devices and will 
routinely inspect for device accountability at the clinical sites participating in this study. The subjects 
will not be responsible for returning the investigational devices. 
8. Ethics 
Trial Conduct 
The study will be conducted according to the Declaration of Helsinki, Protection of Human 
Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical 
Investigators (21 CFR 812). 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other records 
will be identified by a coded number only. All study records will be kept in a locked research 
office with limited access to study personnel and code sheets linking a patient’s name to a 
patient identification number will be stored separately in a secured area within the research 
office. Clinical information will not be released without written permission of the subject, except 
as necessary for monitoring by the FDA. The Investigator must also comply with all applicable 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
privacy regulations (e.g., Health Insurance Portability and Accountability Act of 1996, EU Data 
Protection Directive 95/46/EC). 
Good clinical practice (GCP) is an international quality standard that is provided by International 
Conference of Harmonization (ICH), an international body that defines a set of standards, which 
governments can then transpose into regulations for clinical trials of medications as well as 
medical devices involving human subjects.  
GCP guidelines are important as they provide the necessary enforcement of ethics of a clinical 
study, protection of human rights for the subjects (such as voluntariness) and assurance of the 
safety and efficacy of investigational products. High standards are required in terms of 
comprehensive documentation for the clinical protocol, record keeping (paper and electronic 
which includes computers and software), training, and facilities. Quality assurance and 
inspections ensure that these standards are achieved and maintained.  
GCP guidelines include standards on how clinical trials should be conducted, define the roles 
and responsibilities of clinical trial sponsors, clinical research investigators, and monitors. As a 
research site, we follow the ICH-GCP guidelines. Our GCP includes review of each case to 
determine whether or not the patient would be a good candidate for a clinical trial and if there is 
an appropriate clinical trial for the patient. Important aspects include adequate time for the 
person to review the consent form and have all questions answered, voluntarily give consent 
and know that they can withdraw at any time. Maintaining the subject’s privacy and 
confidentiality is handled by assigning a subject number for each study participant. Research 
staff responsibilities include: adherence to the protocol, proper documentation, accuracy of data 
and appropriate handling of the study product.  
Institutional Review Board Review 
The protocol and consent form will be reviewed and approved by the IRB/IEC of each 
participating center prior to study initiation. Serious adverse experiences regardless of causality 
will be reported to the IRB/IEC in accordance with the standard operating procedures and 
policies of the IRB/IEC, and the Investigator will keep the IRB/IEC informed as to the progress 
of the study. The Investigator will obtain assurance of IRB/IEC compliance with regulations. 
Any documents that the IRB/IEC may need to fulfill its responsibilities (such as protocol, protocol 
amendments, Investigator’s Brochure, consent forms, information concerning patient 
recruitment, payment or compensation procedures, or other pertinent information) will be 
submitted to the IRB/IEC. The IRB/IECs written unconditional approval of the study protocol and 
the informed consent form will be in the possession of the Investigator before the study is 
initiated. The IRB/IECs unconditional approval statement will be transmitted by the Investigator 
to Hologenix contact prior to the shipment of study supplies to the site. This approval must refer 
to the study by exact protocol title and number and should identify the documents reviewed and 
the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without prior 
written IRB/IEC approval except when necessary to eliminate immediate hazards to the patients 
or when the change(s) involves only logistical or administrative aspects of the study. Such 
modifications will be submitted to the IRB/IEC and written verification that the modification was 
submitted and subsequently approved should be obtained.  

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
The IRB/IEC must be informed of revisions to other documents originally submitted for review; 
serious and/or unexpected adverse experiences occurring during the study in accordance with 
the standard operating procedures and policies of the IRB; new information that may affect 
adversely the safety of the patients of the conduct of the study; an annual update and/or request 
for re-approval; and when the study has been completed. 
Any amendment to the protocol will be written by the investigator and Hologenix contact. 
Protocol amendments cannot be implemented without prior written IRB/IEC approval except as 
necessary to eliminate immediate safety hazards to patients. A protocol amendment intended 
to eliminate an apparent immediate hazard to patients may be implemented immediately, 
provided the IRBs are notified within five working days. 
Informed Consent 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US 
Code of Federal Regulations for Protection of Human Subjects (21 CFR 50.25 [a,b], CFR 50.27, 
and CFR Part 56, Subpart A), the Health Insurance Portability and Accountability Act (HIPAA, if 
applicable), and local regulations. 
Subjects cannot be asked to sign the Informed Consent form until the study has been fully 
approved by the investigational site’s IRB and the Sponsor has received and reviewed the 
specific IRB approved Informed Consent form to be used by the site. The potential subject shall 
be given adequate time to read the consent form, have the study procedures explained, 
including risks and benefits, as well as alternative procedures, prior to signing the Informed 
Consent form. An example of the Informed Consent form for this study is provided in Appendix 
1: Informed Consent Form. The consent form must be read by the subject, the subject’s 
questions answered, and the form signed by the subject before the treatment can be performed. 
All subjects are to receive copies of their signed consent form. The date the subject signs the 
consent form is to be recorded on CRF. 
Coverage of Expenses 
Subject Compensation 
Subjects will be paid 35 dollars for each week of participation in the study for each completed 
study visit. Payment will be made after each visit or within 30 days of the ending of their 
participation in the study. All subjects participating in this study will be provided with the Study 
Device listed in this protocol at no cost to them.  
Cost to Subjects 
There will be no cost incurred by the subject for participating in this study. All noted procedures 
are considered standard of care (SOC) and will be billed to the patient’s insurance or whatever 
program the patient uses. 
Confidentiality 
Protected health information (PHI) of clinical investigation Subjects are kept as confidential as 
possible in accordance with the Health Insurance Portability and Accountability Act of 1996 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
(HIPAA). Members of the study team who will have access to the PHI information include the 
following: Research staff at UT Southwestern Hospital, UT Southwestern Wound Clinic, 
Parkland Wound Clinic, Parkland Inpatient Hospital, Sponsor (Hologenix, LLC), and any outside 
labs/facilities that may handle specimens etc. should be named here as well. When appropriate, 
specimens and data will only have subject ID. However, confidentiality cannot be assured. 
9. Data Handling and Record Keeping 
Source Documents 
The investigator must maintain detailed source documents on all subjects who are enrolled or 
who undergo screening in the study. Source documents include subject medical records, 
hospital charts, clinic charts, investigator subject trial files, as well as the results of diagnostic 
tests (e.g., laboratory tests, hemodynamic studies). 
The following minimum information should be entered into the subject’s medical record: 
• 
The date the subject entered the trial 
• 
The IRB number and the name of the Sponsor 
• 
The date that Informed Consent was obtained 
• 
Evidence that the subject meets the trial eligibility requirements (e.g., medical history, 
study procedures and/or evaluations) 
• 
The dates of all trial related subject visits 
• 
Procedures performed that may affect clinical care 
• 
Use of any concurrent medications (antibiotics, antifungals and other anti-infective 
therapies) 
• 
Documentation of specific device used 
• 
Occurrence and status of any adverse events (AEs) 
• 
The date the subject exited the trial and a notation as to whether the subject completed 
the trial or was discontinued. 
 
Data Collection 
The investigator must maintain detailed records on all subjects who sign the Informed Consent 
Form and begin the pre-procedure evaluation. Data for enrolled subjects will be transcribed on 
to CRFs provided by the Sponsor. All data should be transcribed completely, promptly and 
legibly. Corrections should be made in a manner that does not obscure or eliminate the original 
error, by striking through the original data with one line, and initialing and dating the change, 

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
along with the reason for the change (if not obvious). Original CRF pages will be collected by 
the Sponsor or Sponsor’s designee after they are reviewed by the study monitor. The 
investigator should maintain a copy of all completed CRFs from this trial. 
Trial exit forms will be completed for all enrolled subjects, regardless if they did or did not 
complete the trial (e.g., subject discontinuation, trial termination). 
Record Retention 
All records relating to the conduct of this trial are to be retained by the investigator until notified 
by the Sponsor or Sponsor’s designee that the records may be destroyed. 
10. Quality Control and Quality Assurance 
Site Training 
Research staff training involves being credentialed at our institution and other affiliates, CITI 
training, IATA training, training provided by Sponsors, in-house training and protocol training. 
Staff attend the monthly IRB presentations which keeps researchers up to date on regulatory 
news. Required self-training using a binder which contains information on background & 
regulations for research, IRB processes, review of historical cases and glossary of terms and a 
check off sheet for staff. Staff are also encouraged to seek out seminars, webinars & 
conferences that will further their education in research and area of indication (podiatry). The 
binder will be updated on an annual basis and when new information or changes occur to any 
regulations or guidelines. 
Investigator Training 
Investigator Responsibilities 
The investigators are responsible for ensuring that this study is conducted according to this 
protocol and applicable regulations and that signed Informed Consent is obtained from each 
subject prior to his inclusion in this study. It is the investigator’s responsibility to ensure that all 
staff assisting with this study have the appropriate qualifications and are fully instructed on the 
study procedures and respect subject confidentiality, as specified in the Investigator Agreement 
with the Sponsor 
Investigator Records 
Standardized Case Report Forms (CRFs) will be used to collect complete and accurate records 
of the clinical data generated from this study according to Good Clinical Practices (GCP) 
requirements. The investigators are responsible for collecting and accurately recording the 
clinical data generated for this study. Investigators are also responsible for maintaining records 
as required by FDA per Title 21 Code of Federal Regulations (CFR) §812.140. 
Investigator Reports 
The investigator will be responsible for providing the following reports, in accordance with 
CFR§812.150, to the Sponsor for this study: 

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Celliant Clinical Trial Protocol 
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Protocol #: HGX2020-01 
 
 
• 
Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs): 
The investigators will report by telephone, email or fax any SAEs or UADEs as soon as 
possible, within 24 hours of the investigator becoming aware of the event, to the Sponsor 
and the IRB. The Serious Adverse Event form is to be completed to document the SAE 
and it is to be faxed or express mailed to the Sponsor and the IRB within ten working 
days of the event. 
• 
Withdrawal of Approval: If an IRB withdraws the approval to conduct this study for any 
reason, the investigator will notify the Sponsor as soon as possible, but in no event later 
than five working days after the withdrawal of the approval 
• 
Progress Reports: The investigator will submit progress reports on the investigation to 
the Sponsor and the reviewing IRB at regular intervals, but in no event less often than 
yearly. 
• 
Deviations from the Investigational Plan: The investigator must notify the Sponsor and 
the reviewing IRB of any deviation from the Investigational Plan to protect the life or 
physical well-being of a subject in an emergency. This notice must occur as soon as 
possible, but in no case longer than five working days following the occurrence of the 
deviation. 
• 
Informed Consent: If the investigator uses a device without obtaining informed consent, 
the investigator shall report the use to the Sponsor and the IRB within 5 working days 
after the use occurs. 
• 
Final Report: Within three months after the termination or completion of the study or the 
investigator’s part in the study, the investigator shall submit a final report to the Sponsor 
and the IRB. 
• 
Other Reports: Upon request from the IRB or the FDA, the investigator shall provide 
accurate, complete and current information about any aspect of the study. 
Each investigator is responsible for ensuring that the study is conducted according to this 
protocol and that signed Informed Consent is obtained from each subject prior to their inclusion 
in this study. 
11. Adverse Events and Serious Adverse Events 
General 
All observed or volunteered adverse events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections.  
For all adverse events, the investigator must pursue and obtain information adequate both to 
determine the outcome of the adverse event and to assess whether it meets the criteria for 
classification as a serious adverse event requiring immediate notification to the Hologenix 
contact. For all adverse events, sufficient information should be obtained by the investigator to 
determine the causality of the adverse event. The investigator is required to assess causality. 
For adverse events with a causal relationship to the device, follow-up by the investigator is 

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Celliant Clinical Trial Protocol 
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Protocol #: HGX2020-01 
 
 
required until the event or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and the Hologenix contact concurs with that assessment. 
Adverse Event Reporting 
For serious adverse events, the reporting period to Hologenix or its designated representative 
begins from the time that the subject provides informed consent, which is obtained prior to the 
subject’s participation in the study, i.e., prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product. Any serious adverse event occurring any time after 
the reporting period must be promptly reported if a causal relationship to investigational product 
is suspected. Adverse events (serious and non-serious) should be recorded on the CRF from 
the time the subject has undergone one treatment through last subject visit. 
Definition of an Adverse Event (AE) 
An adverse event is any untoward medical occurrence in a clinical investigation subject 
administered a product or medical device; the event need not necessarily have a causal 
relationship with the treatment or usage. Examples of adverse events include but are not limited 
to:   
• 
Abnormal test findings; 
• 
Clinically significant symptoms and signs or diagnosis; 
• 
Changes in physical examination findings; 
• 
Hypersensitivity; 
• 
Progression/worsening of wound. 
 
Protocol Specific AE Definition/Collection 
For the purposes of this study, only AEs that are directly related to the study product, diabetes 
(including labs & kidney function) or wound healing (including infections related to the 
wound) will be collected and reported as these events may affect outcomes and analysis of data. 
AEs not related to the aforementioned product or diagnoses are not relevant to the subject 
outcomes of this research or data analysis (such as nausea, emesis, pain, constipation, 
diarrhea, mood disorders, respiratory diagnoses, cardiac related events, etc). AEs that do not 
fall under this protocol specific definition will be assessed and treated as per standard of care. 
SAEs will be collected as per the usual SAE guidelines (see section on reporting SAEs). In 
addition, planned procedures related to the study wound for a subject during the same 
hospitalization (as these subjects will be recruited while in the hospital because they have an 
infection in their foot wound/ulcer) for incision/debridement/amputation will be considered part 
of their continuation of SOC and not adverse events unless a complication, new infection or new 
wound occurs.  

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Celliant Clinical Trial Protocol 
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Protocol #: HGX2020-01 
 
 
 
Definition of Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is any AE that has any serious unfavorable and unintended 
sign, symptom, or disease temporally associated with the use of the devices, whether or not 
considered related, including those that: 
• 
results in death 
• 
is life-threatening 
• 
requires inpatient hospitalization or causes prolongation of existing hospitalization 
• 
results in persistent or significant disability/incapacity 
• 
is a congenital anomaly/birth defect 
• 
requires intervention to prevent permanent impairment or damage 
Medical and scientific judgment should be exercised in determining whether an event is an 
important medical event. An important medical event may not be immediately life-threatening 
and/or result in death or hospitalization. However, the important medical event should be 
reported as serious, if it is determined that the event may jeopardize the subject and/or may 
require intervention to prevent one of the other adverse event outcomes.  
Causality Assessment of Adverse Events 
The investigator’s assessment of causality must be provided for all adverse events (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the serious adverse reporting requirements 
if applicable. An investigator’s causality assessment is the determination of whether there exists 
a reasonable possibility that the cleared medical device caused or contributed to an adverse 
event. If the investigator does not know whether or not medical device caused the event, then 
the event will be handled as “related to medical device” for reporting purposes. (see Section on 
Reporting Requirements). If the investigator's causality assessment is "unknown but not related 
to investigational product", this should be clearly documented on study records.  
In addition, if the investigator determines a serious adverse event is associated with study 
procedures, the investigator must record this causal relationship in the source documents and 
CRF, as appropriate, and report such an assessment in accordance with the serious adverse 
event reporting requirements, if applicable. 
Adverse Event Severity Assessment 
The Investigator will provide an assessment of the severity of each adverse reaction by 
recording a severity rating on the appropriate SAE reporting page of the subject’s file. Severity, 
which is a description of the intensity of manifestation of the SAE, is distinct from seriousness, 
which implies a patient outcome or SAE-required treatment measure associated with a threat to 
life or functionality. Severity will be assessed according to the following scale. 

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Celliant Clinical Trial Protocol 
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If required on the adverse event case report forms, the investigator will use the 
adjectives MILD, MODERATE, or SEVERE to describe the maximum intensity of 
the adverse event. For purposes of consistency, these intensity grades are defined 
as follows: 
MILD 
Does not interfere with subject's usual function. 
MODERATE Interferes to some extent with subject's usual function. 
SEVERE 
Interferes significantly with subject's usual function. 
Note the distinction between the severity and the seriousness of an adverse event. A severe 
event is not necessarily a serious event. For example, a headache may be severe (interferes 
significantly with subject's usual function) but would not be classified as serious unless it met 
one of the criteria for serious adverse events, listed above. 
Withdrawal Due to Adverse Events (See Also Section on Subject Withdrawal) 
Withdrawal due to adverse event should be distinguished from withdrawal due to insufficient 
response, according to the definition of adverse event noted earlier, and recorded on the 
appropriate adverse event CRF page.  
When a subject withdraws due to a serious adverse event, the serious adverse event must be 
reported in accordance with the reporting requirements defined below. 
Eliciting Adverse Event Information 
The investigator is to report all directly observed adverse events and all adverse events 
spontaneously reported by the study subject. In addition, each study subject will be questioned 
about adverse events by a member of the research staff. 
Reporting Requirements 
Each adverse event is to be assessed to determine if it meets the criteria for serious adverse 
events. If a serious adverse event occurs, expedited reporting will follow local and international 
regulations, as appropriate. 
Serious Adverse Event Reporting Requirements 
If a serious adverse event occurs, Hologenix is to be notified within 24 hours of awareness of 
the event by the investigator. In particular, if the serious adverse event is fatal or life-threatening, 
notification to Hologenix must be made immediately, irrespective of the extent of available 
adverse event information. This timeframe also applies to additional new information (follow-up) 
on previously forwarded serious adverse event reports as well as to the initial and follow-up 
reporting of Exposure during pregnancy cases.  
In the rare event that the investigator or member of the research team does not become aware 
of the occurrence of a serious adverse event immediately (e.g., if an outpatient study subject 

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permission from the Sponsor. 
 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
initially seeks treatment elsewhere), the investigator or member of the research team is to report 
the event within 24 hours after learning of it and document the time of his/her first awareness of 
the adverse event. 
For all serious adverse events, the investigator is obligated to pursue and provide information 
to Hologenix in accordance with the timeframes for reporting specified above. In addition, an 
investigator may be requested by Hologenix to obtain specific additional follow-up information 
in an expedited fashion. This information may be more detailed than that captured on the 
adverse event case report form. In general, this will include a description of the adverse event 
in sufficient detail to allow for a complete medical assessment of the case and independent 
determination of possible causality. Information on other possible causes of the event, such as 
concomitant medications and illnesses must be provided. In the case of a subject death, a 
summary of available autopsy findings and/or a copy of the death certificate must be submitted 
as soon as possible to Hologenix or its designated representative.  
All AEs/SAEs should be followed until resolution. 
Non-Serious Adverse Event Reporting Requirements 
All adverse events will be reported on the adverse event page(s) of the CRF. It should be noted 
that the form for collection of serious adverse event information is not the same as the adverse 
event CRF. Where the same data are collected, the forms must be completed in a consistent 
manner. For example, the same adverse event term should be used on both forms. Adverse 
events should be reported using concise medical terminology on the CRFs as well as on the 
form for collection of serious adverse event information. 
Reporting Requirements to Regulatory Authorities 
Adverse events reporting, including suspected serious unexpected adverse reactions, will be 
carried out in accordance with applicable local regulations. 
12. Committees 
Data and Safety Monitoring Board 
The study will be under the oversight of an independent DSMB that will assess the accumulated 
safety data on an ongoing basis. The role and responsibilities of the DSMB will be predefined in 
the DSMB charter.  
13. Publication Policy 
The preparation and submittal for publication of manuscripts containing the study results shall be in 
accordance with a process determined by mutual written agreement among the investigator and the 
Hologenix contact. The publication or presentation of any study results shall comply with all 
applicable privacy laws, including, but not limited to, the Health Insurance Portability and 
Accountability Act of 1996.  

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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
14. Bibliography 
1. 
Block, P., The diabetic foot ulcer: a complex problem with a simple treatment approach. Milit 
Med, 1981. 146: p. 644-646. 
2. 
Smith, D., M. Weinberger, and B. Katz, A controlled trial to increase office visits and reduce 
hospitalization in diabetic patients. J General Int Med, 1987. 2: p. 232-238. 
3. 
Gibbons, G. and G.M. Eliopoulos, Infection of the Diabetic Foot, in Management of Diabetic Foot 
Problems, Kozak GP  Hoar CS  Rowbotham JL, Editor. 1984, WB Saunders: Philadelphia. p. 
97-102. 
4. 
National Diabetes Advisory Board, The national long-range plan to combat diabetes. 1987, 
National Institutions of Health: Bethesda. 
5. 
Most, R.S. and P. Sinnock, The epidemiology of lower extremity amputations in diabetic 
individuals. Diabetes Care, 1983. 6: p. 87-91. 
6. 
Van Houtum, W.H., et al., Reduction in Diabetes-Related Lower-Extremity Amputations in the 
Netherlands: 1991-2000. Diabetes Care, 2004. 27(5): p. 1042-1046. 
7. 
van Houtum, W.H. and L.A. Lavery, Regional variation in the incidence of diabetes-related 
amputations in the Netherlands. Diabetes Research and Clinical Practice, 1996. 31: p. 125-132. 
8. 
Bild, D.E., et al., Lower extremity amputations in people with diabetes: epidemiology and 
prevention. Diabetes Care, 1989. 12: p. 24-29. 
9. 
Rutkow, I.M. and P.H. Marlboro, Orthopaedic operations in the United States, 1979-1983. J 
Bone Joint Surg, 1986. 68A: p. 716-719. 
10. 
Ashry, H.R., et al., Hospital charges and length of stay for diabetes related amputations in 
minorities. Diabetes, 1996. 45(S2): p. 25A. 
11. 
Gottrup, F., Oxygen in wound healing and infection. World J Surg, 2004. 28(3): p. 312-5. 
12. 
Allen, D.B., et al., Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. 
Arch Surg, 1997. 132(9): p. 991-6. 
13. 
Kumari, R., et al., Impaired wound healing after cerebral hypoxia-ischemia in the diabetic 
mouse. J Cereb Blood Flow Metab, 2007. 27(4): p. 710-8. 
14. 
Schreml, S., et al., Oxygen in acute and chronic wound healing. Br J Dermatol, 2010. 163(2): p. 
257-68. 
15. 
Kalliainen, L.K., et al., Topical oxygen as an adjunct to wound healing: a clinical case series. 
Pathophysiology, 2003. 9(2): p. 81-87. 
16. 
Padberg, F.T., et al., Transcutaneous oxygen (TcPO2) estimates probability of healing in the 
ischemic extremity. J Surg Res, 1996. 60(2): p. 365-9. 
17. 
Kabon, B. and A. Kurz, Optimal perioperative oxygen administration. Curr Opin Anaesthesiol, 
2006. 19(1): p. 11-8. 
18. 
Niinikoski, J., Hyperbaric oxygen therapy of diabetic foot ulcers, transcutaneous oxymetry in 
clinical decision making. Wound Repair Regen, 2003. 11(6): p. 458-61. 
19. 
Niinikoski, J.H., Clinical hyperbaric oxygen therapy, wound perfusion, and transcutaneous 
oximetry. World J Surg, 2004. 28(3): p. 307-11. 
20. 
Hopf, H.W. and M.D. Rollins, Wounds: an overview of the role of oxygen. Antioxid Redox Signal, 
2007. 9(8): p. 1183-92. 

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permission from the Sponsor. 
 
40 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
21. 
Kurz, A., D.I. Sessler, and R. Lenhardt, Perioperative normothermia to reduce the incidence of 
surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature 
Group. N Engl J Med, 1996. 334(19): p. 1209-15. 
22. 
Greif, R., et al., Supplemental perioperative oxygen to reduce the incidence of surgical-wound 
infection. N Engl J Med, 2000. 342(3): p. 161-7. 
23. 
Belda, F.J., et al., Supplemental perioperative oxygen and the risk of surgical wound infection: 
a randomized controlled trial. JAMA, 2005. 294(16): p. 2035-42. 
24. 
Hopf, H.W., et al., Wound tissue oxygen tension predicts the risk of wound infection in surgical 
patients. Arch Surg, 1997. 132(9): p. 997-1004; discussion 1005. 
25. 
Nakada, T., et al., Therapeutic outcome of hyperbaric oxygen and basic fibroblast growth factor 
on intractable skin ulcer in legs: preliminary report. Plast Reconstr Surg, 2006. 117(2): p. 646-
51; discussion 652-3. 
26. 
Sheikh, A.Y., et al., Hyperoxia improves microvascular perfusion in a murine wound model. 
Wound Repair Regen, 2005. 13(3): p. 303-8. 
27. 
Knighton, D.R., I.A. Silver, and T.K. Hunt, Regulation of wound-healing angiogenesis-effect of 
oxygen gradients and inspired oxygen concentration. Surgery, 1981. 90(2): p. 262-70. 
28. 
Klemetti, E., S. Rico-Vargas, and P. Mojon, Short duration hyperbaric oxygen treatment effects 
blood flow in rats: pilot observations. Lab Anim, 2005. 39(1): p. 116-21. 
29. 
Said, H.K., et al., Transdermal sustained-delivery oxygen improves epithelial healing in a rabbit 
ear wound model. Arch Surg, 2005. 140(10): p. 998-1004. 
30. 
Sheikh, A.Y., et al., Effect of hyperoxia on vascular endothelial growth factor levels in a wound 
model. Arch Surg, 2000. 135(11): p. 1293-7. 
31. 
Chen, S.J., et al., Effects of hyperbaric oxygen therapy on circulating interleukin-8, nitric oxide, 
and insulin-like growth factors in patients with type 2 diabetes mellitus. Clin Biochem, 2007. 
40(1-2): p. 30-6. 
32. 
Garcia-Botello, S.A., et al., Randomized clinical trial to evaluate the effects of perioperative 
supplemental oxygen administration on the colorectal anastomosis. Br J Surg, 2006. 93(6): p. 
698-706. 
33. 
Gordillo, G.M., et al., Topical oxygen therapy induces vascular endothelial growth factor 
expression and improves closure of clinically presented chronic wounds. Clin Exp Pharmacol 
Physiol, 2008. 35(8): p. 957-64. 
34. 
Sen, C.K., The general case for redox control of wound repair. Wound Repair Regen, 2003. 
11(6): p. 431-8. 
35. 
Zhao, L.L., et al., Effect of hyperbaric oxygen and growth factors on rabbit ear ischemic ulcers. 
Arch Surg, 1994. 129(10): p. 1043-9. 
36. 
Inoue, S. and M. Kabaya, Biological activities caused by far-infrared radiation. Int J Biometeorol, 
1989. 33(3): p. 145-50. 
37. 
Vatansever, F. and M.R. Hamblin, Far infrared radiation (FIR): its biological effects and medical 
applications. Photonics Lasers Med, 2012. 4: p. 255-266. 
38. 
Hamada Y, T.F., Matsumoto T, et al, Effects of far infrared ray n Hela cells and WI-38 cells. 
International Congress Series, 2003. 1255: p. 339-341. 
39. 
Masuda, A., et al., The effects of repeated thermal therapy for patients with chronic pain. 
Psychother Psychosom, 2005. 74(5): p. 288-94. 

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permission from the Sponsor. 
 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
40. 
Ou, S.M., et al., Far-infrared therapy as a novel treatment for encapsulating peritoneal sclerosis. 
Am J Gastroenterol, 2014. 109(12): p. 1957-9. 
41. 
Toyokawa, H., et al., Promotive effects of far-infrared ray on full-thickness skin wound healing 
in rats. Exp Biol Med (Maywood), 2003. 228(6): p. 724-9. 
42. 
Yu, S.Y., et al., Biological effect of far-infrared therapy on increasing skin microcirculation in rats. 
Photodermatol Photoimmunol Photomed, 2006. 22(2): p. 78-86. 
43. 
Worobets J, S.E., Stefanyshyn D, Apparel with Far Infrared Radiation for Decreasing an 
Athlete's Oxygen Consumption during Submaximal Exercise. Research Journal of Textile and 
Apparel 2015. 19(3): p. 45-51. 
44. 
Sheppard, A.R., M.L. Swicord, and Q. Balzano, Quantitative evaluations of mechanisms of 
radiofrequency interactions with biological molecules and processes. Health Phys, 2008. 95(4): 
p. 365-96. 
45. 
Aijima, R., et al., The thermosensitive TRPV3 channel contributes to rapid wound healing in oral 
epithelia. FASEB J, 2015. 29(1): p. 182-92. 
46. 
Cals-Grierson, M.M. and A.D. Ormerod, Nitric oxide function in the skin. Nitric Oxide, 2004. 
10(4): p. 179-93. 
47. 
Miyamoto, T., et al., TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis 
in the skin. Nat Commun, 2011. 2: p. 369. 
48. 
Davis, J., et al., A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound 
healing in vivo. Dev Cell, 2012. 23(4): p. 705-15. 
49. 
Ogita, S., et al., Effects of far-infrared radiation on lactation. Ann Physiol Anthropol, 1990. 9(2): 
p. 83-91. 
50. 
Ko, G.D. and D. Berbrayer, Effect of ceramic-impregnated "thermoflow" gloves on patients with 
Raynaud's syndrome: randomized, placebo-controlled study. Altern Med Rev, 2002. 7(4): p. 
328-35. 
51. 
Gordon IL, C.S., Vangel M, Hamblin MR, Effect of Shirts with 42% Celliant® Fiber on tcPO2 
Levels and Grip Strength in Healthy Subjects: A Placebo-controlled Clinical Trial. J Textile Sci 
Eng, 2019(9). 
52. 
Washington K, W.J., Thein MS, Lavery LA, Hamblin MR and Gordon IL, Randomized Controlled 
Trial Comparing the Effects of Far-Infrared Emitting Ceramic Fabric Shirts and Control Polyester 
Shirts on Transcutaneous PO2. J Textile Sci Eng, 2018(8). 
53. 
York, R.M. and I.L. Gordon, Effect of optically modified polyethylene terephthalate fiber socks 
on chronic foot pain. BMC Complement Altern Med, 2009. 9: p. 10. 
54. 
Sciences., I.o.C.M.M.C.A.o.C.M., The Test Report on the Impacts of Subject Socks with the 
Application of Celliant® Technical Fibers on Transcutaneous Oxygen Pressure on a Man’s Foot. 
2012. 
55. 
Gordon IL, C.M., Transcutaneous Oxygen Tension (tcP O2) as a Primary Endpoint to Assess 
the Efficacy of an Optically Active Vasoactive Garment. 2012. 
56. 
McClue, G.M., Holofiber Study Of Thirteen (13) Healthy Subjects. 2005. 
57. 
Lavery, L., Holofiber Blood Flow Studies. 2003. 
58. 
Matthew A. Pooley, D.M.A., Haskell W. Beckham, and James F. Brennan, Engineered emissivity 
of textile fabrics by the inclusion of ceramic particles. Opt. Express, 2016. 24: p. 10556-10564. 

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permission from the Sponsor. 
 
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Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
59. 
David M. Anderson, J.R.F., Matthew A. Pooley, Scott Seidel, Michael R. Hamblin, Haskell W. 
Beckham, and James F. Brennan, Infrared radiative properties and thermal modeling of 
ceramic-embedded textile fabrics. Biomed. Opt. Express, 2017. 8: p. 1698-1711. 
60. 
White, A., Measuring Pain. Acupuncture in Medicine, 1998. 16(2): p. 1. 
 
 

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15. Appendix 2 – Diabetic Foot Ulcer Scale – Short Form 
 
 

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Celliant Clinical Trial Protocol 
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Protocol #: HGX2020-01 
 
 
Diabetic Foot Ulcer Scale - Short Form  
INSTRUCTIONS:  
These questions ask about the effect foot ulcers may have on your daily life and well-being. 
Please read each question carefully and think about the effect of your foot ulcers.  
Answer every question by circling one number on each line. If you are unsure about how to 
answer a question, please give the best answer you can.  
Diabetic Foot Ulcer - Short Form  
1. How much have your foot ulcers:  
 
Not 
at all  
A little 
bit  
Moder- 
ately  
Quite 
a bit  
A great 
deal  
a) stopped you from doing the hobbies and 
recreational activities that you enjoy  
1  
2  
3  
4  
5  
b) changed the kinds of hobbies and 
recreational activities that you enjoy doing  1  
2  
3  
4  
5  
c) stopped you from going away for a 
weekend, vacation, or holiday  
1  
2  
3  
4  
5  
d) made you choose a different kind of 
weekend, vacation, or holiday than you 
would have preferred  
1  
2  
3  
4  
5  
e) meant you had to spend more time 
planning and organizing leisure activities  
1  
2  
3  
4  
5  
 
 

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Celliant Clinical Trial Protocol 
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Protocol #: HGX2020-01 
 
 
2. Because of your foot ulcers, how often have you felt:  
 
None of the 
time  
A little of 
the time  
Some of the 
time  
Most of the 
time  
All of the 
time  
a) fatigued or tired  
1  
2  
3  
4  
5  
b) drained  
1  
2  
3  
4  
5  
c) that you had 
difficulty sleeping  
1  
2  
3  
4  
5 
d) pain while walking 
or standing  
1  
2  
3  
4  
5  
e) pain during the 
night  
1 
2 
3 
4 
5 
 
 

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Celliant Clinical Trial Protocol 
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Protocol #: HGX2020-01 
 
 
3. Because of your foot ulcers, how often have you:  
 
None of 
the time  
A little 
of the 
time  
Some of 
the time  
Most of 
the time  
All of 
the 
time  
a) had to depend on others to help 
you look after yourself (like 
washing and dressing)  
1  
2  
3  
4  
5  
b) had to depend on others to do 
household chores (like cooking, 
cleaning or laundry)  
1  
2  
3  
4  
5  
c) had to depend on others for 
getting out of the house  
1  
2  
3  
4  
5  
d) had to spend more time 
planning or organizing your daily 
life  
1  
2  
3  
4  
5  
e) felt that doing anything took 
longer than you would have liked  1  
2  
3  
4  
5  
 
 

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Celliant Clinical Trial Protocol 
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4. Because of your foot ulcers, have you felt:  
Not at 
all  
Slightly  Moder- 
ately  
Quite a 
bit  
Extre- 
mely  
a) angry that you were not able to do 
what you wanted  
1  
2  
3  
4  
5  
b) frustrated by others doing things for 
you when you would rather do them 
yourself  
1  
2  
3  
4  
5  
c) frustrated because you were not 
able to do what you wanted  
1  
2  
3  
4  
5  
d) worried your ulcer(s) will never heal 1  
2  
3  
4  
5  
e) worried you may have to have an 
amputation  
1  
2  
3  
4  
5  
f) worried about injury to your feet  
1  
2  
3  
4  
5  
g) depressed that you were not able 
to do what you wanted  
1  
2  
3  
4  
5  
h) worried about getting ulcers in the 
future  
1  
2  
3  
4  
5  
i) angry this has happened to you  
1  
2  
3  
4  
5  

STU2020-1386, Lavery, FormA3-ResearchProtocol-v11.08.22, Mod_10, 01-03-23 
 
This document contains information that is confidential and proprietary. The contents of this document may not be copied without written 
permission from the Sponsor. 
 
48 
 
Celliant Clinical Trial Protocol 
PI: Lavery 
Protocol #: HGX2020-01 
 
 
j) frustrated because you have 
difficulty getting around  
1  
2  
3  
4  
5  
5. Because of your foot ulcers, how often were you bothered by:  
 
None 
of the 
time  
A little of 
the time  
Some of 
the time  
Most 
of the 
time  
All of 
the 
time  
a) having to keep weight off your foot 
ulcer  
1  
2  
3  
4  
5  
b) the amount of time involved in 
caring for your foot ulcer (including 
dressing changes, waiting for the 
home health care nurse, and keeping 
the ulcer clean)  
1  
2  
3  
4  
5  
c) the appearance, odor or weeping of 
your ulcer  
1  
2  
3  
4  
5  
d) having to depend on others to help 
care for your foot ulcer  
1  
2  
3  
4  
5  
THANK YOU FOR COMPLETING THIS QUESTIONNAIRE  
DFS-SF © 1999 Mapi Research Trust, All rights reserved  
DFS-SF - United States/English - Version of 22 Feb 08 - Mapi Research Institute. ID4557 / DFS-SFeng-USq_author