Protocol summary

Study aim
Determining the safety and feasibility of bi-layered allogenic cultured keratinocyte and fibroblast skin substitute application in the treatment of chronic diabetic foot ulcer
Design
In this first phase, single group, not randomized open-label clinical trial study, five patients will be enrolled in regular order according to standard protocols. The first patient will be monitored for one month, and if cell therapy is safe, the next patient will be Entered the study. Again, provided the treatment is safe during this period, the second and then the third patient will enter the study. In the absence of severe and life-threatening complications, subsequent patients will be included in the study.
Settings and conduct
Intervention site and patient visit: Diabetic foot ulcer clinic of Tehran University of Medical Sciences Intervention: Debridement and skin substitute grafting to the dimensions of patients' wounds in the wound area
Participants/Inclusion and exclusion criteria
Inclusion criteria: Patients with chronic diabetic foot ulcer on the plantar surface of the foot that is grade 2A in University of Texas score with the size of 2 to 20 cm2, that not treated despite two weeks of standard treatment, and with Conscious consent Exclusion criteria: Pregnant patients, with weakened immune systems or uncontrolled underlying disease, evidence of infection, osteomyelitis, or gangrene
Intervention groups
The intervention group consisted of diabetic patients with chronic diabetic foot ulcers that receive skin substitute transplantation at the beginning and on the 14th day if the wound did not heal.
Main outcome variables
Evaluation of side effects, including short-term and long-term, systemic or local, severe or mild, and related and unrelated side effects of cell therapy at times 3, 7, 14, 18, 21, 28 days, and 6, 8, 12, 16, 20 and 24 weeks after the intervention

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20080728001031N33
Registration date: 2022-07-03, 1401/04/12
Registration timing: prospective

Last update: 2022-07-03, 1401/04/12
Update count: 0
Registration date
2022-07-03, 1401/04/12
Registrant information
Name
Nasser Aghdami
Name of organization / entity
Royan Institute
Country
Iran (Islamic Republic of)
Phone
+98 21 2356 2000
Email address
nasser.aghdami@royaninstitute.org
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2022-07-23, 1401/05/01
Expected recruitment end date
2023-07-23, 1402/05/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The Safety & Feasibility of Bi-Layered Allogeneic Cultured Keratinocyte and Fibroblast Skin Substitute Application for Chronic Diabetic Foot Ulcers: Clinical Trial Phase I
Public title
The Safety of Skin Substitute Application for Chronic Diabetic Foot Ulcer
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age between 18-80 years Both gender Type I or II diabetes ABI ≥ 0.8 HgA1c ≤ 8% Palpable pulse Ulcer university of Texas score=2A Ulcer ≥ 4w presented ulcer >2w under standard care Ulcer on plantar surface of foot Ulcer Size ≥ 2.0 cm2 Ulcer depth ≤ 1cm
Exclusion criteria:
Pregnancy Malignancy not in remission for 5 y Severe malnutrition (serum albumin <2.0) Alcohol or drug abuse Random BS ≥ 450 mg/dL Urine ketones Use of corticosteroids, immunosuppressive or cytotoxic agents, Coumadin History of bleeding disorder Positive viral markers (HIV, HBV, HCV, HTLV, CMV) Participation in another study in previous 30 d Conditions compromise ability to complete the study Clinical evidence of infection at the beginning of the treatment phase Evidence of osteomyelitis Evidence of gangrene Charcot deformity Nondiabetic etiology Tunnels or sinus tracts Ulcer >20 cm2 (longest dimension > 5 cm) Elective osseous procedures to the study foot within 30 d before Increased or decreased in size by ≥ 20% in screening period Severe hepatic impairment (LFT ≥ 2 * ULN) or renal impairment (Cr> 2.5 mg/dl)
Age
From 18 years old to 80 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size: 5
Randomization (investigator's opinion)
Not randomized
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Research ethics committees of Royan institute-Academic center for education, culture and research
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Ghasem Soleymani Highway
City
Tehran
Province
Tehran
Postal code
1951883831
Approval date
2022-06-18, 1401/03/28
Ethics committee reference number
IR.ACECR.ROYAN.REC.1401.026

Health conditions studied

1

Description of health condition studied
Type 1 diabetes mellitus with foot ulcer
ICD-10 code
E10.621
ICD-10 code description
Type 1 diabetes mellitus with foot ulcer

2

Description of health condition studied
Type 2 diabetes mellitus with foot ulcer
ICD-10 code
E11.621
ICD-10 code description
Type 2 diabetes mellitus with foot ulcer

Primary outcomes

1

Description
short-term or long term, systemic or local, severe or mild, and related or unrelated to cell therapy adverse effects
Timepoint
Before the intervention, at the time of intervention, 3, 7, 14, 18, 21, 28 days and 6, 8, 12, 16, 20 and 24 weeks after the intervention
Method of measurement
Physician assessment by physical examination

Secondary outcomes

1

Description
Ulcer healing rate
Timepoint
12th week after intervention
Method of measurement
ImageJ software

2

Description
50% improvement in wound size
Timepoint
12th week after intervention
Method of measurement
ImageJ software

3

Description
mean rate of wound healing during the first 12 weeks
Timepoint
Days 3, 7, 14, 18, 21 and 28 as well as weeks 6, 8 and 12 after the intervention
Method of measurement
Physician evaluation and solar calendar

4

Description
The rate of recurrence of the wound at the site of the previous healing
Timepoint
24th week after the intervention
Method of measurement
Physician evaluation and examination

Intervention groups

1

Description
Intervention group: Name of substance used: Bi-layered skin substitute. Chemical composition and its concentration: Allogenic cultured keratinocyte and fibroblast cells. The number of 2 million fibroblast cells per square centimeter on type I bovine collagen bed and then 300,000 keratinocyte cells per square centimeter and a total diameter of 44 square centimeters. Frequency of use: 1 or 2 times. Duration of use: 2 weeks. How to use: A skin replacement graft of the same size as the wound is cut by sterile scissors and placed in the wound area after debridement and then covered with a suitable wound dressing. Manufacturer: ATMP Department of Royan Research Institute.
Category
Treatment - Other

Recruitment centers

1

Recruitment center
Name of recruitment center
Royan Institute
Full name of responsible person
Ensiyeh Hajizadeh Saffar
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2233 9942
Email
hajizadeh.ehs@gmail.com

2

Recruitment center
Name of recruitment center
Endocrine research center of Tehran university of medical sciences
Full name of responsible person
Mohammadreza Amini
Street address
Endocrine Research Center, 5th Floor, Dr. Shariati Hospital, North Kargar St., Tehran
City
Tehran
Province
Tehran
Postal code
1411713139
Phone
+98 21 8863 1298
Email
mramini@tums.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
ATI tech pharmed
Full name of responsible person
Dr. Ensiyeh Hajizadeh Saffar
Street address
Golbarg alley. Royan alley. E Hafez St. Bani Hashem St. Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665659911
Phone
+98 21 2233 9942
Email
hajizadeh.ehs@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
ATI tech pharmed
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other

Person responsible for general inquiries

Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Shayan Farzanbakhsh
Position
researcher
Latest degree
Medical doctor
Other areas of specialty/work
General Practitioner
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
Shayan.farzanb@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Ensiyeh Hajizadeh Saffar
Position
Associate professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Biotechnology
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2233 9942
Email
hajizadeh.ehs@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Hoda Madani
Position
researcher
Latest degree
Medical doctor
Other areas of specialty/work
General Practitioner
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
hoda62_m@yahoo.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
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