A Randomized Controlled Clinical Trial Comparing High Purity Type-I Collagen-based Skin Substitute to Dehydrated Human Amnion/Chorion Membrane in the Treatment of Diabetic Foot Ulcers
Phase: NA
Conditions: Diabetic Foot Ulcer (DFU)
Sponsor: Adichunchanagiri Institute of Medical Sciences, B G Nagara

 
Title:  
 
A Randomized, Controlled Clinical Trial Comparing the Use of High Purity Type- 
I Collagen-based Skin Substitute vs. Dehydrated Human Amnion/Chorion 
Membrane in the Treatment of Diabetic Foot Ulcers 
 
 
NCT Number:  
               NCT06470087 
 
 Date of the document:  
                31/10/2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 Title: A Randomized, Controlled Clinical Trial Comparing the Use of High Purity Type- 
I Collagen-based Skin Substitute vs. Dehydrated Human Amnion/Chorion Membrane 
in the Treatment of Diabetic Foot Ulcers 
 
Introduction 
Chronic wounds, especially diabetic foot ulcers (DFUs), place a significant financial strain on 
healthcare systems. In the United States, the estimated annual cost for treating these wounds 
is about $30 billion. DFUs are the most prevalent form of lower extremity wounds, making 
up roughly 80% to 85% of such cases. Annually, between 6.5 and 7 million individuals in the 
U.S. are affected by chronic DFUs. With an aging population and increasing incidence of risk 
factors such as obesity and congestive heart failure, the prevalence of DFUs is expected to 
rise. 
Chronic diabetic foot ulcers (DFUs) are linked to considerable suffering and a decline in 
quality of life, as the healing process is typically slow and painful. Even in optimal 
conditions, these ulcers can take weeks or months to recover, often experiencing a frustrating 
pattern of slow healing and repeated breakdown. Wound care specialists frequently encounter 
patients who have suffered from these ulcers for years, with some needing amputation as the 
only solution for pain relief. 
Type-I collagen, when full, purified, and uncross-linked, offers 3,000 receptor sites per 
molecule for growth factors like fibroblasts to adhere to, making it an ideal matrix for wound 
healing. Type-I collagen shows 97% similarity across species, while Type-II and Type-III 
collagen only have 80% similarity within the same species. For instance, Type-I collagen in 
humans is quite similar to that in cows or birds. Furthermore, Type-I collagen is the least 
likely to provoke an immune response due to its lack of the sulfur-containing amino acid 
cysteine. In contrast, Type-II and Type-III collagen contain more cysteine, making them more 
immunogenic. 
The objective of this study is to evaluate and compare the safety and effectiveness of High 
Purity Type-I Collagen-based Skin Substitute (HPTC) with Dehydrated Human 
Amnion/Chorion Membrane (dHACM) for treating diabetic foot ulcers (DFUs). This 
randomized, controlled clinical trial seeks to provide valuable insights into the best treatment 
strategy for enhancing healing outcomes and reducing the challenges posed by chronic DFUs. 
 
Materials and Methods 
Study will be carried out as a randomized, controlled open-label study to evaluate the safety 
and effectiveness of High Purity Type-I Collagen-based Skin Substitute (HPTC) compared to 
Dehydrated Human Amnion/Chorion Membrane (dHACM) for treating diabetic foot ulcers 
(DFUs). The trial will include patients with DFUs treated by wound care specialists at 
Adichunchanagiri Institute of Medical Sciences, B. G. Nagara, under the supervision of 
primary investigator Dr Naveen N. Informed consent will be obtained from all participants 
prior to any study-related procedures, and each patient will sign an Institutional Ethics 
Committee/Investigational Review Board (IEC/IRB)-approved consent form. 
The investigator will comply with regulatory guidelines and Good Clinical Practice (GCP) in 
obtaining and documenting informed consent. All study products will be produced, handled, 

and stored in accordance with Good Manufacturing Practices (GMP). Strict patient 
confidentiality protocols will be maintained throughout the study. 
 
 
 
Patient Screening and Eligibility 
The study population will consist of patients seeking treatment for DFUs. Eligible patients 
will be those willing to participate and comply with scheduled visits on days 7, 10, 14, 17, 21, 
and 28. The study will include two phases: screening and treatment. The screening phase 
aimed to determine patient eligibility for the treatment phase. The inclusion and exclusion 
criteria are detailed in Table 1. During screening, a series of assessments will be conducted, 
including demographics, medical history, concomitant medications, vital signs, physical 
examination, leg ulcer history, clinical infection signs at the ulcer site. 
 
Study Treatment: 
The treatment phase of the study will commence with a series of evaluations to ensure 
patients remained eligible. Participants who will continue to meet the inclusion criteria after 
the screening phase will be randomly assigned to one of two groups: 
1. Standard of Care (SOC) with High Purity Type-I Collagen-based Skin Substitute 
(HPTC). 
2. Standard of Care (SOC) with Dehydrated Human Amnion/Chorion Membrane 
(dHACM). 
Neither the patients nor the clinicians will be blinded to group assignments. The 
randomization will follow a balanced schedule, using permuted blocks of 12. When a patient 
will be ready for randomization, the study site will contact a representative from the sponsor, 
who will open a sequentially numbered opaque envelope to disclose the group assignment, 
maintaining allocation concealment. 
Throughout the 4-week treatment phase, patients will be reassessed on days 7, 10, 14, 17, 21, 
and 28. The SOC dressing applied in both groups consisted of a three-layer system: 
 
First layer: Non-adherent, porous paraffin gauze. 
 
Second layer: Absorbent gauze pads. 
 
Third layer: Soft roll and Crepe bandage. 
Note: 
a. 
2 sizes of HPTC used: 
i. 
0.8 in x 1.6 in or 2 cm x 4 cm (8 sq cm) 
ii. 
1.6 in x 1.6 in or 4 cm x 4 cm (16 sq cm) 
b. 
2 sizes of dHACM used: 
i. 
5 cm x 5 cm (25 sq cm) 
ii. 
8 cm x 6 cm (48 sq cm) 
 
If the study ulcer was found to be 100% re-epithelialized during the visit, no further study 
procedures will be conducted at that time. The patient will then be scheduled for a follow-up 
visit after one week to confirm the healing. 

If full healing was not achieved, an evaluation will be carried out to check for any signs of 
clinical infection. If an infection is confirmed, treatment with topical antimicrobials or oral 
antibiotics will be permitted, though the use of topical antibiotics will be prohibited. 
After this infection assessment, the ulcer would be cleaned, photographed, and debrided at 
the investigator's discretion to ensure a clean and granulating wound base with minimal 
adherent slough. The Standard of Care (SOC) will be then re-applied, and patients will be 
instructed to keep the bandage dry. Additionally, they will be advised to contact or return to 
the study site if the bandage became soiled or removed. 
 
Study Completion: 
Patients will complete the study 4 weeks after their initial treatment visit. However, if a 
patient's study ulcer healed before the 4-week period, they will be considered to have 
completed the study at the time of full healing. 
Complete healing will be defined as 100% re-epithelialization of the ulcer with no drainage. 
Throughout the study, patients will retain the right to decline participation or withdraw at any 
time without prejudice. 
In the event of a patient's withdrawal, their last recorded wound measurement will be carried 
forward to determine the change in wound size and calculate their final outcome. 
 
Study Outcomes: 
Primary Endpoint: 
 
The primary outcome of the study will be the proportion of subjects who achieved 
improvement in wound healing, as observed on days 7, 10, 14, 17, 21, and 28. The 
wound closure of the target ulcer will be continuously monitored until the end of the 
4-week period. 
Secondary Endpoints: 
 
Time to Achieve Complete Wound Closure: Time taken for the target ulcer to 
achieve complete wound closure will be assessed on days 7, 10, 14, 17, 21, and 28. 
 
Percentage Wound Area Reduction: This will be measured weekly on days 7, 10, 
14, 17, 21, and 28 using digital photography. 
 
Mean Number of Repeated Applications of HPTC: The average number of times 
the reapplication of High Purity Type-I Collagen-based Skin Substitute (HPTC) to 
achieve wound closure will be documented as part of the study process. 
Exploratory Endpoint: 
 
The appearance, structural stability, and fragility of the newly formed skin will be 
documented at each visit. Any recurrence of the wound will also be monitored. 
 

Subjects must be at least 18 years of age or 
older. 
A subject known to have a life expectancy 
of less than 6 months. 
Subjects must have a diagnosis of type 1 or 2 
diabetes mellitus. 
If the target ulcer is infected or if there is 
cellulitis in the surrounding skin. 
At enrolment, subjects must have a target 
diabetic foot ulcer with a minimum surface 
area of 5.0 cm² and a maximum surface area 
of 10.0 cm², measured post-debridement 
using a ruler. 
Presence of osteomyelitis or exposed 
bone, probes to bone or joint capsule on 
investigator’s exam, or radiographic 
evidence. 
The target ulcer must have been present for a 
minimum of 4 weeks and a maximum of 52 
weeks of standard care prior to the initial 
screening visit. 
A subject that has an infection in the target 
ulcer that requires systemic antibiotic 
therapy. 
 
The target ulcer must be located on the foot, 
with at least 50% of the ulcer below the 
malleolus. 
A subject receiving immunosuppressants 
(including systemic corticosteroids at 
doses greater than 10 mg of prednisone 
per day or equivalent) or cytotoxic 
chemotherapy. 
The target ulcer must be full thickness on the 
foot or ankle and must not probe to bone. 
Topical application of steroids to the ulcer 
surface within one month of initial 
screening. 
Adequate circulation to the affected foot as 
documented by any of the following methods 
performed within 3 months of the first 
screening visit: a. Transcutaneous Oxygen 
Measurement (TCOM) ≥ 30 mmHg b. Ankle- 
Brachial Index (ABI) between 0.7 and 1.3 c. 
Peripheral Vascular Resistance (PVR): 
Biphasic d. Toe-Brachial Index (TBI) ˃ 0.6 e. 
Alternatively, arterial Doppler ultrasound can 
be performed to evaluate biphasic dorsalis 
pedis and posterior tibial vessels at the level 
of the ankle of the target extremity. 
 
 
 
 
A subject with a previous partial 
amputation on the affected foot is 
excluded if the resulting deformity 
impedes proper offloading of the target 
ulcer. 
If the subject has two or more ulcers, they 
must be separated by at least 2 cm. The 
largest ulcer satisfying the inclusion and 
exclusion criteria will be designated as the 
target ulcer. 
A subject with a glycated hemoglobin 
(HbA1c) greater than or equal to 13%, 
taken at or within 3 months of the initial 
screening visit. 

The subject must consent to using the 
prescribed off-loading method for the 
duration of the study. 
A subject with a serum creatinine ≥ 3.0 
mg/dL within 6 months of the initial 
screening visit. 
The subject must agree to attend the twice- 
weekly/weekly study visits required by the 
protocol. 
A subject with an acute Charcot foot, or an 
inactive Charcot foot, that impedes proper 
offloading of the target ulcer. 
The subject must be willing and able to 
participate in the informed consent process.
Women who are pregnant or considering 
becoming pregnant within the next 6 
months. 
Patients must have read and signed the 
IEC/IRB-approved informed consent form 
(ICF) before screening procedures are 
undertaken. 
 
A subject with end-stage renal disease 
requiring dialysis. 
A subject who participated in a clinical trial 
involving treatment with an investigational 
product within the previous 30 days. 
A subject who, in the opinion of the 
Investigator, has a medical or psychological 
condition that may interfere with study 
assessments. 
A subject treated with hyperbaric oxygen 
therapy or a Cellular and/or Tissue Product 
(CTP) in the 30 days prior to the initial 
screening visit. 
Table 1: Inclusion and Exclusion Criteria 
 
 
Statistical analysis :- 
 
Descriptive statistics will be used to summarize the data. Quantitative data will be presented as 
means or medians, while qualitative data will be expressed as frequencies and percentages. The 
study aims to assess the proportion of study participants achieving wound healing by the end of 
the fourth week. To measure the proportion of participants showing improvement in wound 
healing, observations will be conducted on days 7, 10, 14, 17, 21, and 28. The proportion of 
participants achieving wound healing would be compared between both the groups using Chi-
square/ Fisher's exact test. Additionally, the average reduction in ulcer size from baseline to the 
end of the fourth week will be compared between groups, and the significance of the reduction 
will be analysed using the independent t test/Mann-Whitney U test.