Perianal Fistula in Patients With Crohn's DiseasePhase 1/2NCT05499156
Safety of Injection of Placental Mesenchymal Stem Cell Derived Exosomes for Treatment of Resistant Perianal Fistula in Crohn's Patients
A Phase 1/2 study testing placenal MSC derived exosomes in people with Perianal Fistula in Patients With Crohn's Disease, run by Tehran University of Medical Sciences at 1 site in Iran.
Trial summary
Study aim: Safety of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of perianal fistula in patients with Crohn's disease 2. Efficacy of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of refractory Anal Fistula in patients with Crohn's disease 3. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Perianal Fistula in Patients With Crohn's Disease
- What is being tested?
- placenal MSC derived exosomes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteIran
- Study dates
- 20 Jan 2022to Sep 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18-70 years old
- Occurrence of complex perianal fistula
- Informed consent
Who cannot join
- Active inflammatory bowel disease
- Synchronous perianal abscess
- Alcohol,narcotic and stimulant consumption
- Having active Hepatitis B,C,HIV or TB
- Peregnancy and lactation
- Uncontrolled diabetes mellitus
- Evidence of surgical contraindication
- Psychological disorders and noncooperative patient
Trial locations and contacts
1 site in 1 country.
Iran1 site
Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran
Tehran, 1978775553
About this study
Study aim:
Safety of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of perianal fistula in patients with Crohn's disease 2. Efficacy of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of refractory Anal Fistula in patients with Crohn's disease 3. Fistula changes in MRI studies, 12 weeks after treatment 4. Evaluation of quality of life in perianal fistula patient's questionnaire score before and 12 weeks after treatment
Read more
Participants/Inclusion and exclusion criteria:
inclusion criteria: 1. Age between 18-70 years old 2.Occurrence in patients with Crohn's disease 3. Informed consent Exclusion Criteria: 1. Active inflammatory bowel disease 2. Synchronous perianal abscess 3. Alcohol, narcotics and stimulant consumption 4. Having active Hepatitis B, C, HIV, or TB 5. Pregnancy and lactation 6.Uncontrolled diabetes mellitus 7. Evidence of surgical contraindication 8.Psychological disorders and noncooperative patient
Intervention groups:
Human Placenta Mesenchymal Stem Cells Derived Exosomes injected in fistula tract of patients with complex perianal Fistula in 3 weekly episodes, and it's safety and efficacy were evaluated.
Design:
this study includes two separate groups of cases and controls, each consisting of 40 participants randomly allocated for phase 2 of a clinical trial.
Settings and conduct:
Patients with complex perianal fistula referred to Imam Khomeini hospital will be included in the study if they contain inclusion criteria. The fistula was evaluated by clinical examination, and MRI and patients fill the quality of life questionnaire. Exosome injections are performed weekly for three consecutive weeks. Patients will be reexamined and fill out the questionnaire, and MRI will be done 12 weeks later. Recent findings will compare with the initial data. During this period, patients are examined for complications.
Main outcome variables:
Discharge amount; External orifice re-epithelialization; Inflammation, discharge and abscess larger than 2 cm in MR imaging; Quality of life questionnaire score, Inflammatory markers such as CRP, IL-6, TNF-a, calprotectin
Read the detailed description
All patients who were enrolled in our study had refractory disease. These patients were previously treated and had unhealed cryptoglandular fistulas. The patients who were enrolled in this study were those who did not make any improvement after administration of 10 mg/kg of intravenous infliximab and seton placement. Patients were excluded if they had anti-TNF α treatment for less than six months, had no prior surgical interventions, or had a history of malignancies or immunodeficiency diseases. Pregnant patients were also excluded.
MSCs in third passage 3 were cultured in T175 flasks with D-MEM F12 culture medium (Gibco) supplemented with Pen/Strep, Strep, and 10 % exosome depleted FBS(Gibco) for 48 hours at 37 °C with a CO2 concentration of 5% at and humidity of 90 % humidity. Under 5% CO2. The conditioned media of MSCs (CM) were collected and centrifuged for 10 min at 400×g to eliminate suspended cells, 30 min at 2500×g to remove debris and apoptotic bodies, and then ultracentrifuged for 120 min at 100000×g (Beckman, USA). The supernatants were collected and further ultracentrifuged for 120 min at 100000×g. Then the pellets containing exosomes were dissolved in PBS.
To verify The production of MSC- derived exosomes, vesicle protein content was measured by Bradford colorimetric assay (BCA) from 100 ml of CM. The size distribution of MSC- derived exosomes were determined by dynamic light scattering (DLS). Moreover, to assess the expression of CD9, CD63 and CD81 were confirmed with flow cytometry and western blot., FITC mouse anti-CD63 (BD Pharmingen) and PE mouse anti-CD81 (BD Pharmingen) were used as reagents. Furthermore, the morphology and size of isolated exosomes were assessed using TEM by the previously set protocol in the previous study.
The procedure was undertaken in the operation room, and the patients were NPO 6 hours before the operation with intravenous sedation and oxygen supplementation with a mask. The patients, placed were placed in a lithotomy position. The external fistula opening was inspected, the tract was palpated, and using an Eisenhammer Retractor, the internal orifice was exposed seen. The lot was irrigated with saline several times using a small catheter to clear the pus and fecal material. After irrigation, a flexible fistula probe was inserted into the tract. Using the probe as a guide, we injected 5 mL of exosome solution into the tissue surrounding the lot. The injection depth was about 2about 2-3 mm of the soft tissue and sphincters of the anus. After the injection, the tract probe was extracted, the patients were under observation in the operation recovery rooming room recovery for 3 hours, and vital signs were monitored. The patients were then transferred to the surgery ward and were observed for 48 hours. The patients were again examined under sedation in the operation room for further evaluation six months after injection.
- Being tested
- placenal MSC derived exosomes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placenal MSC derived exosomesOther
placenta-MSCs derived exosomes Exosomes are extracellular vesicles that are 30 to 150 nm in diameter. these vesicles are secreted from various cells. Mesenchymal stem cells exhibit immunomodulatory and anti- inflammatory properties by the use of paracrine effects. Exosomes as a vehicle for signaling, are responsible for a major part of cell to cell signaling. The preclinical animal studies manifested high safety and efficacy for MSC derived exosome treatment on various fistulas and inflammatory bowel disease. In this study we aimed to evaluate the safety and efficacy of PlacentaMSCs derived exosomes in treatment of patients with complex preanal fistula (non-crohn's) in phase I and II of clinical trial
| Study group | Role | What they receive |
|---|---|---|
| exosome therapy | Experimental | placenta-MSCs derived exosomes Exosomes are extracellular vesicles that are 30 to 150 nm in diameter. These vesicles are secreted from various cells. Mesenchymal stem cells exhibit immunomodulatory and anti-inflammatory properties by using paracrine effects. Exosomes, as a vehicle for signaling, are responsible for a significant part of cell-to-cell signaling. The preclinical animal studies manifested high safety and efficacy for MSC-derived exosome treatment on various fistulas and inflammatory bowel disease. In this study, we aimed to evaluate the safety and effectiveness of PlacentaMSCs derived exosomes in the treatment of patients with complex preanal fistula (Crohn's) in phases I and II of the clinical trial Receives: Other: placenal MSC derived exosomes |
| placebo | Experimental | placebo Receives: Other: placenal MSC derived exosomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of injected exosomes
assessing the adverse outcomes after an injection such as acute allergic reactions, systemic effects such as fever, tachycardia, nausea and vomiting, diarrhea, cardinal manifestations, neutropenia, leukopenia, hemolysis, and local reactions such as cellulitis, abscess, skin rash, bleeding, necrosis
Measured: 3 months
clinical Efficacy of injected exosomes
They are assessing the clinical response to therapy which might demonstrate the closure of refractory fistulas. These results include a full fistula closure in clinical observation and radiological assessments by MRI. Clinical improvement can be described as improvements in clinical manifestations such as pain, discharge, and bloody discharges. The fistulae are also assessed with MRI scans.
Measured: 3 months
inflammatory markers
assessing inflammatory markers through laboratory workup, including CRP, IL-6, TNF-a, calprotectin
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2022
- Study start20 Jan 2022
- Primary completionAug 2022 (estimated)
- Study completionSep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Perianal Fistula in Patients With Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study includes two arms. The first one is the cases that are treated with MSC-derived exosomes and the controls do not receive exosomes and are treated with placebo
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tehran University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05499156
- Sponsor's protocol ID
- IRCT20200413047063N3
- Status last verified
- Sep 2021
- First submitted
- 30 May 2022
- Last updated
- 12 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Injection of Placental Mesenchymal Stem Cell Derived Exosomes for Treatment of Resistant Perianal Fistula in Crohn's Patients
- ClinicalTrials.gov ID
- NCT05499156
- Acronym / sponsor ID
- IRCT20200413047063N3
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Tehran University of Medical SciencesUniversity, hospital or other
- Study start
- 20 Jan 2022 (actual)
- Primary completion
- Aug 2022 (estimated)
- Study completion
- Sep 2022 (estimated)
- First posted
- 12 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study aim:
Safety of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of perianal fistula in patients with Crohn's disease 2. Efficacy of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of refractory Anal Fistula in patients with Crohn's disease 3. Fistula changes in MRI studies, 12 weeks after treatment 4. Evaluation of quality of life in perianal fistula patient's questionnaire score before and 12 weeks after treatment
Participants/Inclusion and exclusion criteria:
inclusion criteria: 1. Age between 18-70 years old 2.Occurrence in patients with Crohn's disease 3. Informed consent Exclusion Criteria: 1. Active inflammatory bowel disease 2. Synchronous perianal abscess 3. Alcohol, narcotics and stimulant consumption 4. Having active Hepatitis B, C, HIV, or TB 5. Pregnancy and lactation 6.Uncontrolled diabetes mellitus 7. Evidence of surgical contraindication 8.Psychological disorders and noncooperative patient
Intervention groups:
Human Placenta Mesenchymal Stem Cells Derived Exosomes injected in fistula tract of patients with complex perianal Fistula in 3 weekly episodes, and it's safety and efficacy were evaluated.
Design:
this study includes two separate groups of cases and controls, each consisting of 40 participants randomly allocated for phase 2 of a clinical trial.
Settings and conduct:
Patients with complex perianal fistula referred to Imam Khomeini hospital will be included in the study if they contain inclusion criteria. The fistula was evaluated by clinical examination, and MRI and patients fill the quality of life questionnaire. Exosome injections are performed weekly for three consecutive weeks. Patients will be reexamined and fill out the questionnaire, and MRI will be done 12 weeks later. Recent findings will compare with the initial data. During this period, patients are examined for complications.
Main outcome variables:
Discharge amount; External orifice re-epithelialization; Inflammation, discharge and abscess larger than 2 cm in MR imaging; Quality of life questionnaire score, Inflammatory markers such as CRP, IL-6, TNF-a, calprotectin
Detailed description
All patients who were enrolled in our study had refractory disease. These patients were previously treated and had unhealed cryptoglandular fistulas. The patients who were enrolled in this study were those who did not make any improvement after administration of 10 mg/kg of intravenous infliximab and seton placement. Patients were excluded if they had anti-TNF α treatment for less than six months, had no prior surgical interventions, or had a history of malignancies or immunodeficiency diseases. Pregnant patients were also excluded.
MSCs in third passage 3 were cultured in T175 flasks with D-MEM F12 culture medium (Gibco) supplemented with Pen/Strep, Strep, and 10 % exosome depleted FBS(Gibco) for 48 hours at 37 °C with a CO2 concentration of 5% at and humidity of 90 % humidity. Under 5% CO2. The conditioned media of MSCs (CM) were collected and centrifuged for 10 min at 400×g to eliminate suspended cells, 30 min at 2500×g to remove debris and apoptotic bodies, and then ultracentrifuged for 120 min at 100000×g (Beckman, USA). The supernatants were collected and further ultracentrifuged for 120 min at 100000×g. Then the pellets containing exosomes were dissolved in PBS.
To verify The production of MSC- derived exosomes, vesicle protein content was measured by Bradford colorimetric assay (BCA) from 100 ml of CM. The size distribution of MSC- derived exosomes were determined by dynamic light scattering (DLS). Moreover, to assess the expression of CD9, CD63 and CD81 were confirmed with flow cytometry and western blot., FITC mouse anti-CD63 (BD Pharmingen) and PE mouse anti-CD81 (BD Pharmingen) were used as reagents. Furthermore, the morphology and size of isolated exosomes were assessed using TEM by the previously set protocol in the previous study.
The procedure was undertaken in the operation room, and the patients were NPO 6 hours before the operation with intravenous sedation and oxygen supplementation with a mask. The patients, placed were placed in a lithotomy position. The external fistula opening was inspected, the tract was palpated, and using an Eisenhammer Retractor, the internal orifice was exposed seen. The lot was irrigated with saline several times using a small catheter to clear the pus and fecal material. After irrigation, a flexible fistula probe was inserted into the tract. Using the probe as a guide, we injected 5 mL of exosome solution into the tissue surrounding the lot. The injection depth was about 2about 2-3 mm of the soft tissue and sphincters of the anus. After the injection, the tract probe was extracted, the patients were under observation in the operation recovery rooming room recovery for 3 hours, and vital signs were monitored. The patients were then transferred to the surgery ward and were observed for 48 hours. The patients were again examined under sedation in the operation room for further evaluation six months after injection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- This study includes two arms. The first one is the cases that are treated with MSC-derived exosomes and the controls do not receive exosomes and are treated with placebo
| Arm | Type | Receives |
|---|---|---|
| exosome therapy | Experimental | Other: placenal MSC derived exosomesplacenta-MSCs derived exosomes Exosomes are extracellular vesicles that are 30 to 150 nm in diameter. These vesicles are secreted from various cells. Mesenchymal stem cells exhibit immunomodulatory and anti-inflammatory properties by using paracrine effects. Exosomes, as a vehicle for signaling, are responsible for a significant part of cell-to-cell signaling. The preclinical animal studies manifested high safety and efficacy for MSC-derived exosome treatment on various fistulas and inflammatory bowel disease. In this study, we aimed to evaluate the safety and effectiveness of PlacentaMSCs derived exosomes in the treatment of patients with complex preanal fistula (Crohn's) in phases I and II of the clinical trial |
| placebo | Experimental | Other: placenal MSC derived exosomesplacebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age between 18-70 years old
- Occurrence of complex perianal fistula
- Informed consent
Key exclusion criteria (8 listed)
- Active inflammatory bowel disease
- Synchronous perianal abscess
- Alcohol,narcotic and stimulant consumption
- Having active Hepatitis B,C,HIV or TB
- Peregnancy and lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placenal MSC derived exosomesplacenta-MSCs derived exosomes Exosomes are extracellular vesicles that are 30 to 150 nm in diameter. these vesicles are secreted from various cells. Mesenchymal stem cells exhibit immunomodulatory and anti- inflammatory properties by the use of paracrine effects. Exosomes as a vehicle for signaling, are responsible for a major part of cell to cell signaling. The preclinical animal studies manifested high safety and efficacy for MSC derived exosome treatment on various fistulas and inflammatory bowel disease. In this study we aimed to evaluate the safety and efficacy of PlacentaMSCs derived exosomes in treatment of patients with complex preanal fistula (non-crohn's) in phase I and II of clinical trial | Other | exosome therapy, placebo |
Primary outcome
Safety of injected exosomes
Time frame: 3 months
assessing the adverse outcomes after an injection such as acute allergic reactions, systemic effects such as fever, tachycardia, nausea and vomiting, diarrhea, cardinal manifestations, neutropenia, leukopenia, hemolysis, and local reactions such as cellulitis, abscess, skin rash, bleeding, necrosis
clinical Efficacy of injected exosomes
Time frame: 3 months
They are assessing the clinical response to therapy which might demonstrate the closure of refractory fistulas. These results include a full fistula closure in clinical observation and radiological assessments by MRI. Clinical improvement can be described as improvements in clinical manifestations such as pain, discharge, and bloody discharges. The fistulae are also assessed with MRI scans.
inflammatory markers
Time frame: 3 months
assessing inflammatory markers through laboratory workup, including CRP, IL-6, TNF-a, calprotectin
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing placenal MSC derived exosomes in people with Perianal Fistula in Patients With Crohn's Disease, run by Tehran University of Medical Sciences at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of injected exosomes (time frame: 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2022.