Evaluation of the safety and efficacy of the injection of placenta-derived mesenchymal stromal/stem cell exosomes with and without priming with TNF‐α in patients with complex perianal fistula without a history of CHRONS disease: A double-blinded randomized controlled trial
Evaluation of the safety and efficacy of human placental stromal/mesenchymal stem cells-derived exosomes treated with TNF-α in patients with perianal fistula without underlying disease
Design
Clinical trial with the control group, with factorial groups, double-blind, randomized, phase 1 on 30 patients. The rand function of Excel software was used for randomization.
Settings and conduct
The method of implementing this study (all steps will be done Shariati Hospital):
- Receiving placenta samples
- Isolation of mesenchymal stem cells from the placenta based on GMP and their characterization
- Priming with TNF-α
- Preparing and collecting Conditioned Media
- Isolation of exosomes
- Exosome characterization
- Exosome injection
- Follow-up of patients
Participants/Inclusion and exclusion criteria
Inclusion criteria: sign the informed consent, Patients with complex perianal fistula aged 18-75, Acceptable general health
Exclusion criteria: Patients with underlying diseases that affect the pathophysiology of perianal fistula
Intervention groups
1- The first group will receive the conventional seton along with normal saline injection as a control group for the exosome groups.
2- The second group will receive seton plus injection of untreated exosomes (as a control group for treated exosomes). The number of injections in this group will be 1 time.
3- The third group will receive seton plus an injection of treated exosomes. The number of injections in this group will be 1 time.
Main outcome variables
مورفولوژی سلول های MSC; تمایز MSC به رده‌های مختلف; بیان مارکر CD۳۴ سطح سلول; بیان مارکر CD۴۵ سطح سلول; بیان مارکر CD۴۴ سطح سلول; بیان مارکر CD۹۰ سطح سلول; بیان مارکر CD۱۰۵ سطح سلول; TNF‐α; زنده‌مانی MSCها; توزیع سایز اگزوزوم‌ها; غلظت پروتئین محلول حاوی اگزوزوم‌ها; CBC در بیماران; CRP در بیماران; ESR در بیماران; Calprotectin بیماران; اندکس‌های بهبود در معاینات تحت بیهوشی (EUA)
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20240128060828N1
Registration date:2024-02-02, 1402/11/13
Registration timing:prospective
Last update:2024-02-02, 1402/11/13
Update count:0
Registration date
2024-02-02, 1402/11/13
Registrant information
Name
Hossein Bagheri
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 918 599 8525
Email address
h-bagheri@razi.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2024-02-20, 1402/12/01
Expected recruitment end date
2024-05-21, 1403/03/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of the safety and efficacy of the injection of placenta-derived mesenchymal stromal/stem cell exosomes with and without priming with TNF‐α in patients with complex perianal fistula without a history of CHRONS disease: A double-blinded randomized controlled trial
Public title
Investigating the effect of stromal/mesenchymal stem cell-derived exosomes in patients with perianal fistula
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
sign the informed consent
Patients with complex perianal fistula aged 18-75
Acceptable general health of patients based on physical tests and medical history (absence of diseases or disorders that may interfere with the treatment method evaluated in this study)
Exclusion criteria:
Patients with underlying diseases that affect the pathophysiology of perianal fistula (including IBD, rectovaginal fistula or acute sepsis, uncontrolled diabetes, and active or latent HIV, HBV, or HCV infection)
Patients who need perianal surgery for reasons other than fistula
Major surgeries within 28 days before admission
Use of immune system modulators for reasons other than fistula in patients
Age
From 18 years old to 75 years old
Gender
Both
Phase
1
Groups that have been masked
Outcome assessor
Data analyser
Sample size
Target sample size:
30
Randomization (investigator's opinion)
Randomized
Randomization description
RANDBETWEEN function of Excel software was used for randomization.
In short, cells that contain patients with numbers 1 to 30 with the RANDBETWEEN function [fx = RANDBETWEEN(1, 30)] are selected, and patients are randomly assigned a number based on the mentioned groups. In this way, random numbers 1 to 10 are in the first group, numbers 10 to 20 are in the second group, and numbers 20 to 30 are in the third group.
Blinding (investigator's opinion)
Double blinded
Blinding description
During this study, the data analyst and the clinician will be blinded.
The clinical doctor only received the vial of liquid without the description label, and the patient will be unaware of the type of injected substance (therapeutic or control substance).
Placebo
Used
Assignment
Factorial
Other design features
This study will be conducted as a phase 1 randomized controlled clinical trial in order to check the safety and effectiveness of the treatment method of this study in three groups and with the inclusion of 30 patients (10 patients in each group). During this study, blinding will be done in a double-blind manner, for this purpose, the specialist doctor and the patient will not know about the treatment method used. The groups will be as follows: 1- The first group will receive the conventional seton along with normal saline injection as a control group for the exosome groups. 2- The second group will receive seton plus injection of untreated exosomes (as a control group for treated exosomes). The number of injections in this group will be 1 time. 3- The third group will receive seton plus an injection of treated exosomes. The number of injections in this group will be 1 time.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committees of The Institute of Pharmaceutical Sciences -Tehran University of Medical
Street address
North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1417933431
Approval date
2024-01-20, 1402/10/30
Ethics committee reference number
IR.TUMS.TIPS.REC.1402.155
Health conditions studied
1
Description of health condition studied
Perianal Fistula
ICD-10 code
K60.3
ICD-10 code description
Anal fistula
Primary outcomes
1
Description
Evaluation of any regional undesirable events
Timepoint
Within 48 to 72 hours
Method of measurement
In the form of a phone call and based on the patient's opinion
2
Description
Evaluation of any systemic undsirable events
Timepoint
Within 48 to 72 hours
Method of measurement
In the form of a phone call and based on the patient's opinion
3
Description
Degree of healing recorded by surgeon examination
Timepoint
Examination of the patient's condition during 6 months of follow-up
Method of measurement
by laboratory tests and especially during examination under anesthesia (EUA)
4
Description
Degree of self satisfaction and quality of life recorded by patients
Timepoint
After the termination of the follow-up of the patient's condition
Method of measurement
By using special questionnaires for the health context of 36-Item Short Form Survey (SF-36)
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: Seton (conventional treatment method of perianal fistula) plus injection of untreated exosomes-derived placenta mesenchymal stem cells (as a control group for treated exosomes). The number of injections in this group will be 1 time.
Category
Treatment - Other
2
Description
Intervention group: Seton plus injection of treated exosomes-derived placenta mesenchymal stem cells. The number of injections in this group will be 1 time.
Category
Treatment - Other
3
Description
Control group: conventional seton along with normal saline (as a control group for exosome groups). In order to reduce the difference between the treatment and control groups, it is also necessary to inject normal saline so that the therapeutic effect of the new combined approach can be relied upon.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Shariati Hospital
Full name of responsible person
Nasim Vousooghi
Street address
North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1417933431
Phone
+98 912 372 4378
Email
Dr.n.vosoughi@gmail.com
Web page address
https://isid.research.ac.ir/Nasim_Vousooghi
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Nasim Vousooghi
Street address
North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1417933431
Phone
+98 912 372 4378
Email
Dr.n.vosoughi@gmail.com
Web page address
https://isid.research.ac.ir/Nasim_Vousooghi
Grant name
Not available
Grant code / Reference number
کد و ردیف بودجه در حال حاضر مشخص نشده است.
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Nasim Vousooghi
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1417933431
Phone
+98 912 372 4378
Email
dr.n.vosoughi@gmail.com
Web page address
https://isid.research.ac.ir/Nasim_Vousooghi
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Nasim Vousooghi
Position
Associate professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1417933431
Phone
+98 912 372 4378
Email
dr.n.vosoughi@gmail.com
Web page address
https://isid.research.ac.ir/Nasim_Vousooghi
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Hossein Bagheri
Position
Ph.D Candidate
Latest degree
Master
Other areas of specialty/work
Applied Cell Science (Cell Therapy)
Street address
North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1417933431
Phone
009185998525
Email
h-bagheri@razi.tums.ac.ir
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
Yes - There is 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
Not applicable
Title and more details about the data/document
Because the study is in the preliminary stage and if the study is done, the mentioned sections will be added.
When the data will become available and for how long
The access period starts 6 months after the results are published
To whom data/document is available
All scientists interested in research in this field
Under which criteria data/document could be used
If needed, the sections and documents not provided will be provided.
From where data/document is obtainable
Dr. Nasim Vousooghi - Phone Number: 009123724378 - Email address: dr.n.vosoughi@gmail.com - Postal Address: No. 87, Third floor, Building No.2, School of Advanced Technologies in Medicine, Italia st, Keshavarz blv. Tehran, Iran; Postal Code: 1417755469
What processes are involved for a request to access data/document
After confirming the identity of the person, the documents/data will be provided as soon as possible after the request.