Effects of Exosome Adminstration in Preventing Early Leakage in Rectal Cancer Patients Undergoing Low Anterior Resection

Investigating the Effect of Intraperitoneal Administration of Exosome in Preventing Early Anastomotic Leakage in Rectal Cancer Patients Who Undergo Low Anterior Resection

The goal of this clinical trial is to assess the safety and efficacy of Human Placenta Mesenchymal Stem Cells Derived Exosomes in preventing early anastomosis leak in patients undergoing low anterior resection for rectal cancer. The main question it aims to answer are

Do Mesenchymal Stem Cell-Derived Exosomes prevent early anastomosis leak in patients undergoing low anterior resection for rectal cancer?

If there is a comparison group: Researchers will compare Mesenchymal Stem Cells Derived Exosomes to placebo to see if it can prevent early anastomotic leakage.

Participants will receive intraperitoneal Mesenchymal Stem Cells Derived Exosomes at the end of their surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Biological: Mesenchymal Stem Cells Derived Exosomes; Other: Placebo

Detailed Description

Anastomotic leakage remains one of the most severe complications following colorectal surgery, leading to increased morbidity, prolonged hospitalization, and reduced quality of life. Despite advances in surgical techniques and perioperative care, the incidence of early anastomotic leaks persists. Practical strategies to reduce this risk are crucial for improving patient outcomes.

Recent studies have highlighted the potential role of mesenchymal stem cell-derived exosomes in enhancing tissue repair and modulating inflammation. These extracellular vesicles, derived from human placenta mesenchymal stem cells (hPMSC), contain bioactive molecules such as proteins, lipids, and RNA that facilitate cellular communication and promote healing processes. Preclinical research suggests that exosomes can support anastomotic healing by reducing local inflammation.

This study aims to evaluate the safety and efficacy of intraperitoneal administration of hPMSC-derived exosomes in preventing early anastomotic leakage in patients undergoing low anterior resection (LAR) for rectal cancer. We hypothesize that the exosome treatment will significantly reduce the incidence of anastomotic leaks compared to placebo, thereby improving postoperative recovery and reducing hospital stay.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Seyed Mohsen Ahmadi Tafti, MD; Phone Number: +98(912)2109773; Email: smahmadit@sina.tums.ac.ir

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1419733141
    • Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

-Patients with Stage II-III rectal cancer who underwent neoadjuvant chemoradiation therapy and are candidates for low anterior resection surgery

Exclusion Criteria:

• Patients who need emergency surgery (presenting with peritonitis or signs of obstruction)
• Patients with apparent malnutrition or patients who have serum albumin levels of less than 3 g/dl
• Patients who receive corticosteroids ( an equivalent dose of prednisolone 5 mg/day or more)
• Patients with chronic pulmonary disease
• Patients who need more than two units of blood transfusion perioperatively

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal Stem Cells Derived Exosomes; 10 patients in this arm will receive Mesenchymal Stem Cells Derived Exosomes at the end of their low anterior resection surgery	Biological: Mesenchymal Stem Cells Derived Exosomes; Mesenchymal Stem Cells Derived Exosomes will be administered intraperitoneally to patients at the end of their surgery
Placebo Comparator: Placebo; 10 patients in this arm will receive placebo at the end of their low anterior resection surgery	Other: Placebo; 10 patients will receive intraperitoneal placebo at the end of their surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with early anastomotic leakage	Failed surgical anastomosis after surgery measured with interview and physical examinations in follow-up sessions in clinic	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean serum and peritoneal Interleukin-6 and Tumor necrosis factor-alpha levels in participants	The level of serum and peritoneal inflammatory markers in postoperative days measured with laboratory tests	1 month
Anastomosis integrity in Colonoscopy exam	A colonoscopy will be conducted one month after surgery to assess the integrity of the colorectal anastomosis, detect early signs of local recurrence, identify polyps, and monitor for any postoperative complications such as strictures or inflammatory changes. Baseline colonoscopies will be compared with post-surgical colonoscopy at one month. This outcome will help determine the efficacy of surgical intervention and guide future surveillance strategies in rectal cancer management.	1 month
Hospitalization length of stay	The number of days that the patient in hospitalized postoperatively	1 month

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Study Director: Seyed Mohsen Ahmadi Tafti, MD, Colorectal Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences,

Publications and helpful links

General Publications

• Lipska MA, Bissett IP, Parry BR, Merrie AE. Anastomotic leakage after lower gastrointestinal anastomosis: men are at a higher risk. ANZ J Surg. 2006 Jul;76(7):579-85. doi: 10.1111/j.1445-2197.2006.03780.x.
• Platell C, Barwood N, Dorfmann G, Makin G. The incidence of anastomotic leaks in patients undergoing colorectal surgery. Colorectal Dis. 2007 Jan;9(1):71-9. doi: 10.1111/j.1463-1318.2006.01002.x.
• Choi HK, Law WL, Ho JW. Leakage after resection and intraperitoneal anastomosis for colorectal malignancy: analysis of risk factors. Dis Colon Rectum. 2006 Nov;49(11):1719-25. doi: 10.1007/s10350-006-0703-2.
• Barnhoorn MC, Wasser MNJM, Roelofs H, Maljaars PWJ, Molendijk I, Bonsing BA, Oosten LEM, Dijkstra G, van der Woude CJ, Roelen DL, Zwaginga JJ, Verspaget HW, Fibbe WE, Hommes DW, Peeters KCMJ, van der Meulen-de Jong AE. Long-term Evaluation of Allogeneic Bone Marrow-derived Mesenchymal Stromal Cell Therapy for Crohn's Disease Perianal Fistulas. J Crohns Colitis. 2020 Jan 1;14(1):64-70. doi: 10.1093/ecco-jcc/jjz116.
• Tashak Golroudbari H, Banikarimi SP, Ayati A, Hadizadeh A, Khorasani Zavareh Z, Hajikhani K, Heirani-Tabasi A, Ahmadi Tafti M, Davoodi S, Ahmadi Tafti H. Advanced micro-/nanotechnologies for exosome encapsulation and targeting in regenerative medicine. Clin Exp Med. 2023 Oct;23(6):1845-1866. doi: 10.1007/s10238-023-00993-7. Epub 2023 Jan 27.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 20, 2024
• First Submitted That Met QC Criteria: August 2, 2024
• First Posted (Estimated): August 5, 2024

Study Record Updates

• Last Update Posted (Estimated): August 5, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: IR.TUMS.IKHC.REC.1403.114

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