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

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

Study Overview

• Status: Recruiting
• Conditions: Fistula Perianal
• Intervention / Treatment: Other: placenta-MSCs derived exosomes

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1419733141
    • Recruiting
    • Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran
    • Contact: Seyed Mohsen Ahmadi Tafti, Assistant Professor; Phone Number: +98(912)2109773; Email: smahmadit@sina.tums.ac.ir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2021
• Primary Completion (Anticipated): December 22, 2022
• Study Completion (Anticipated): March 22, 2023

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Rectal Diseases; Intestinal Fistula; Digestive System Fistula; Fistula; Rectal Fistula
• Other Study ID Numbers: IRCT20211212053361N1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No