Safety and Efficacy of Injection of Human Placenta Mesenchymal Stem Cells Derived Exosomes for Treatment of Complex Anal Fistula

Study Overview
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Brief Summary
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Study aim: Safety of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of complex Anal Fistula 2.Efficacy of Human Placenta Mesenchymal Stem Cells Derived Exosomes for treatment of refractory Anal Fistula 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 of complex perianal fistula 3.Informed consent Exclusion Criteria: 1.Active inflammatory bowel disease 2.Synchronous perianal abscess 3.Alcohol,narcotic and stimulant consumption 4.Having active Hepatitis B,C,HIV or TB 5.Peregnancy 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 was evaluated. Design: this study includes two separate groups of cases and controls each consisting of 40 participants randomly allocated for the phase 2 of 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 consecutive three weeks. Patients will reexamined and fill the questionnaire and MRI will done 12 weeks later. Recent findings will compare with the initial data. During this period, patients are examine 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

Official Title
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Safety and Efficacy of Injection of Human Placenta Mesenchymal Stem Cells Derived Exosomes for Treatment of Complex Anal Fistula

Conditions
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Fistula Perianal

Intervention / Treatment
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* Other: placenta-MSCs derived exosomes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-70 years old Occurrence of complex perianal fistula Informed consent Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: exosome cases<br>The patients whose fistula is treated by exosome (40 patients). | Other: placenta-MSCs derived exosomes<br>* 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 Placenta-MSCs derived exosomes in treatment of patients with complex preanal fistula (non-crohn's) in phase I and II of clinical trial.<br>|
| Placebo Comparator: Controls<br>The patients whose fistula is treated with conventional treatment plan (40 patients). | Other: placenta-MSCs derived exosomes<br>* 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 Placenta-MSCs derived exosomes in treatment of patients with complex preanal fistula (non-crohn's) in phase I and II of clinical trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of injected exosomes | assessing the adverse outcomes after injection such as acute allergic reactions | 3 months | 
| clinical Efficacy of injected exosomes | assessing the clinical response to therapy which might demonstrate itself as closure of refractory fistulas | 3 months | 
| inflammatory markers | assessing inflammatory markers through laboratory workup including CRP, IL-6, TNF-a, calprotectin. | 3 months |