Washed Microbiota Transplantation for The Treatment of Oncotherapy-Related Intestinal Complications

Efficacy and Safety of Washed Microbiota Transplantation for The Treatment of Oncotherapy-Related Intestinal Complications

Gut microbiota, known as "unrecognized organs", is closely related to the occurrence and development of tumors. Cancer is thought to occur secondary to local chronic inflammation. And some bacteria, such as Helicobacter pylori, also have direct genotoxicity, changing intracellular signaling pathways and thus causing abnormal cell growth. Systemic intestinal dysbiosis may lead to cancer, and fecal microbiota transplantation (FMT) can be a new weapon in anti-cancer treatment.Washed microbiota transplantation (WMT), a new stage of FMT, is based on the automatic microfiltration machine (GenFMTer, Nanjing, China) and the following repeated centrifugation plus suspension with support from specific facilities. The investigators conducted a prospective, one-arm, open-label study on the efficacy and safety of WMT in the treatment of oncotherapy-related complications. This study aimed to exploring the therapeutic potential of WMT in the treatment of oncotherapy-related intestinal complications and improving the quality of life of patients.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Intestinal Complications
• Intervention / Treatment: Procedure: Washed Microbiota Transplantation (WMT)

Detailed Description

Gut microbiota, known as "unrecognized organs", is closely related to the occurrence and development of tumors. Cancer is thought to occur secondary to local chronic inflammation. And some bacteria, such as Helicobacter pylori, also have direct genotoxicity, changing intracellular signaling pathways and thus causing abnormal cell growth. Systemic intestinal dysbiosis may lead to cancer, and fecal microbiota transplantation (FMT) can be a new weapon in anti-cancer treatment. The reduction of intestinal flora diversity may lead to intestinal dysbiosis, thereby reducing the body immunity and promoting the formation and development of neoplasm. It has been reported that FMT can be used to treat melanoma, liver cancer and prostate cancer after immunotherapy failed. But the mechanism of gut microbiota on the tumor itself remains to be further explored. In 2019, an Italian study reports the efficacy of FMT for diarrhea induced by tyrosine kinase inhibitors in the treatment of renal cell carcinoma, suggesting the therapeutic potential of gut microbiota for tumor-related gastrointestinal complications [1].

Fecal Microbiota transplantation (FMT), the most classic way to treat diseases using gut microbiota [2], refers to the transplantation of functional microbiota in the feces of healthy people into the intestines of patients. It can reconstruct the overall gut microbiota of patients, thus treating gastrointestinal diseases and external gastrointestinal diseases of patients. In 2013, FMT was for the first time coined into the treatment guidelines on recurrent CDI, and now it plays an important role as a key treatment for clostridium difficile infection [3]. Washed microbiota transplantation (WMT), a new stage of FMT, is based on the automatic microfiltration machine (GenFMTer, Nanjing, China) and the following repeated centrifugation plus suspension with support from specific facilities. Compared with manual FMT, WMT can reduce the rate of adverse events (such as fever, diarrhea, abdominal pain, abdominal distension, nausea and vomiting, etc.) without affecting the efficacy. In addition, Zhang et al. have proved that WMT is better than the manual preparation of FMT in improving safety, enriching the precise amount of microbiota and quality controllable in practice [4]. In December 2019, A panel of 28 experts from 22 hospitals or institutes in 15 cities has contributed to the "Nanjing consensus on methodology of washed microbiota transplantation" according to the international standards, and the consensus is published in Chinese Medical Journal in July 2020 [5].

Therefore, the investigators conducted a prospective, one-arm, open-label study on the efficacy and safety of WMT in the treatment of oncotherapy-related intestinal complications. This study aimed to exploring the therapeutic potential of WMT in the treatment of oncotherapy-related intestinal complications and improving the quality of life of patients.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Faming Zhang, MD,PhD; Phone Number: 086-25-58509883; Email: fzhang@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Recruiting
      • Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University
      • Contact: Faming Zhang, MD, PhD; Phone Number: 086-25-58509883; Email: fzhang@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age ≥18 years old; 2. Diagnosed as malignant tumor; 3. Patients who underwent cancer-related treatment suffering from gastrointestinal symptoms(e.g., abdominal pain, diarrhea, abdominal distension, and difficulty defecating) occurred after standard tumor therapy (such as chemotherapy, radiation, immunotherapy, surgical treatment, etc.); 4. Estimated time of survival ≥ 3 months, and vital signs were stable); 5. Physically qualified and intended to undergo FMT;

Exclusion Criteria:

• 1. Patients who were pregnant or nursing; 2. Patients who were unable or unwilling to undergo a gastroscopy or colonoscopy; 3. Patients with cardiopulmonary failure; 4. Antibiotics, PPI, probiotics, and other drugs that alter gut microbiota were used in the previous week; 5. history of inflammatory bowel disease and intestinal symptoms unrelated to tumor treatment; 6.Serious uncontrolled diseases and acute infectious diseases；

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Washed Microbiota Transplantation (WMT); Patients undergo once WMT a day for three consecutive days.	Procedure: Washed Microbiota Transplantation (WMT); Washed microbiota suspension (5u) delivered through nasogastric tube, nasojejunal tube or oral. Dose and frequency: 5u, three times.; Other Names: fecal microbiota transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scores of gastrointestinal symptoms	Gastrointestinal symptoms will be evaluated according to NCI-CTC 5.0	8 weeks
Stool frequency and consistency	Stool frequency and consistency will be evaluated according to The Bristol Stool Form Scale (BSFS).	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	New onset of symptoms and the exacerbation of previous symptoms were recorded as adverse events (AEs)	1 year
Karnofsky Performance Status (KPS) scale	Changes in functional status of patients will be assessed according to the Karnofsky Performance Status (KPS) scale (ranging from 0 [dead] to 100 [normal activity, no evidence of disease])	8 weeks

Collaborators and Investigators

• Sponsor: The Second Hospital of Nanjing Medical University

Publications and helpful links

General Publications

• Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 Apr;108(4):478-98; quiz 499. doi: 10.1038/ajg.2013.4. Epub 2013 Feb 26.
• Zhang T, Lu G, Zhao Z, Liu Y, Shen Q, Li P, Chen Y, Yin H, Wang H, Marcella C, Cui B, Cheng L, Ji G, Zhang F. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein Cell. 2020 Apr;11(4):251-266. doi: 10.1007/s13238-019-00684-8. Epub 2020 Jan 9.
• Prisciandaro M, Ratta R, Massari F, Fornarini G, Caponnetto S, Iacovelli R, De Giorgi U, Facchini G, Scagliarini S, Sabbatini R, Caserta C, Peverelli G, Mennitto A, Verzoni E, Procopio G. Safety and Efficacy of Cabozantinib for Metastatic Nonclear Renal Cell Carcinoma: Real-world Data From an Italian Managed Access Program. Am J Clin Oncol. 2019 Jan;42(1):42-45. doi: 10.1097/COC.0000000000000478. Erratum In: Am J Clin Oncol. 2019 Apr;42(4):412.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2021
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Fecal Microbiota Transplantation; Intestinal dysbiosis; Washed Microbiota Transplantation; Oncotherapy
• Other Study ID Numbers: Cancer-CN-202010

Drug and device information, study documents

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