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

Official title

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

Overview

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.

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.

Interventions

• Biological Mesenchymal Stem Cells Derived Exosomes
  Mesenchymal Stem Cells Derived Exosomes will be administered intraperitoneally to patients at the end of their surgery
• Other Placebo
  10 patients will receive intraperitoneal placebo at the end of their surgery

Primary outcome measures

• Number of patients with early anastomotic leakage [Time frame: 1 month]

Secondary outcome measures (3)

• Mean serum and peritoneal Interleukin-6 and Tumor necrosis factor-alpha levels in participants [Time frame: 1 month]
• Anastomosis integrity in Colonoscopy exam [Time frame: 1 month]
• Hospitalization length of stay [Time frame: 1 month]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Iran · 1 center

• Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Scienc — Tehran

Publications

• 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. PMID 17181849
• 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. PMID 16813622
• 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. PMID 17051321
• 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 PMID 31197361
• 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. PMID 36705868

Identifiers

NCT: NCT06536712 · IR.TUMS.IKHC.REC.1403.114

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗