Washed Microbiota Transplantation for Clostridioides Difficile Infection

Clostridioides Difficile Infection Clinical Trial

Official title:

Washed Microbiota Transplantation for Clostridioides Difficile Infection: a Real World Research

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06106698
• Other study ID #: WMT-RWS-CDI
• Status: Recruiting
• Start date: July 22, 2023
• Est. completion date: December 2029

Study information

• Verified date: July 2023
• Source: The Second Hospital of Nanjing Medical University
• Contact: Faming Zhang, PhD
• Phone: 086-025-58509883
• Email: fzhang[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a real-world study to explore the safety and the efficacy of washed microbiota transplantation （WMT） for patients with Clostridioides Difficile Infection （CDI）.

Description:

At least 12 subjects who meet all the inclusion criteria but do not meet any exclusion criteria will be enrolled in this study. Data of demographic characteristics, intestinal symptoms, medicine treatment usage and clinical outcomes will be collected. After treatment, they will enter the follow-up period （at least for 4-week post-WMT）for safety and efficacy evaluation. Subjects with no response and recurrence will receive salvage therapy, and the extended follow-up period will be performed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2029
• Est. primary completion date: July 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 100 Years

Eligibility

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to enter the study:

1. At the time of informed consent, male or non-pregnant or non-lactating female.

2. The diagnostic criteria for C. difficile infection are met during screening:

1. Medical records confirming CDI prior to screening (laboratory tests are positive for Clostridium difficile or its toxin): Clostridium difficile toxin test is positive (determined by EIisa test), or colonoscopy indicates pseudomembranous enteritis; Or Glutamate dehydrogenase positive, toxin negative, there are obvious causes and diarrhea.

2. CDI-related diarrhea episodes, i.e., defecation =3 times/day for at least two consecutive days with unformed stools (Bristol score 6-7).

3. The subject or his/her legal representative gives informed consent, fully understands the purpose of the study, is able to communicate effectively with the investigator, and comprehends and complies with the requirements set forth in the study.

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria must be excluded from the study:

1. Subjects with immune deficiencies (such as HIV infection, or neutrophils <0.5×109/L in absolute value, or lymphocytes <0.5×109/L, etc.), or on immunosuppressants, or on medium to high doses of steroid hormones (=20g/d of prednisone or equal doses of steroid hormones).

2. There is rectal outlet obstruction (such as rectal mucosal prolapse) or significant intestinal stenosis assessed by the investigator and colonic transendoscopic enteral tubing cannot be performed.

3. Confirmed or clinically suspected infection with pathogenic microorganisms other than Clostridium difficile prior to screening.

4. Have had major abdominal surgery (other than laparoscopic gallbladder or appendectomy), previous partial or total colectomy, previous partial small intestinal resection, or previous gastroduodenal surgery within 6 months prior to screening.

5. At the time of screening, the subject or his/her legal representative refuses to take effective contraception within 3 months after the last treatment.

6. According to the judgment of the investigator, the subjects are not suitable to participate in this clinical study, or participation in this clinical study cannot guarantee the rights and interests of the subjects.

Related Conditions & MeSH terms

• Clostridioides Difficile Infection
• Clostridium Infections
• Communicable Diseases
• Infections

Intervention

Other:
• WMT
Washed microbiota transplantation refers to the infusion of washed microbiota from healthy donor into patients' gastrointestinal tract. Participants will receive one dose of WMT for CDI. During follow-up, those who have non-response or CDI recurrence within 4-week post-WMT will receive rescue WMT.

Locations

Country	Name	City	State
China	The second affiliated hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Second Hospital of Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (9)

Ademe M. Benefits of fecal microbiota transplantation: A comprehensive review. J Infect Dev Ctries. 2020 Oct 31;14(10):1074-1080. doi: 10.3855/jidc.12780. — View Citation

Antharam VC, Li EC, Ishmael A, Sharma A, Mai V, Rand KH, Wang GP. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013 Sep;51(9):2884-92. doi: 10.1128/JCM.00845-13. E — View Citation

Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, Putignani L, Fischer M, Keller JJ, Costello SP, Sokol H, Kump P, Satokari R, Kahn SA, Kao D, Arkkila P, Kuijper EJ, Vehreschild MJG, Pintus C, Lopetuso L, Masucci L, Scaldaferri F, Terv — View Citation

Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt TJ. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015 May 5;162(9):630-8. doi: 10.7326/M14-2693. — View Citation

Guh AY, Mu Y, Winston LG, Johnston H, Olson D, Farley MM, Wilson LE, Holzbauer SM, Phipps EC, Dumyati GK, Beldavs ZG, Kainer MA, Karlsson M, Gerding DN, McDonald LC; Emerging Infections Program Clostridioides difficile Infection Working Group. Trends in U — View Citation

Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. Correction to: ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2022 Feb 1;117(2):358. doi: 10. — View Citation

Ng SC, Kamm MA, Yeoh YK, Chan PKS, Zuo T, Tang W, Sood A, Andoh A, Ohmiya N, Zhou Y, Ooi CJ, Mahachai V, Wu CY, Zhang F, Sugano K, Chan FKL. Scientific frontiers in faecal microbiota transplantation: joint document of Asia-Pacific Association of Gastroent — View Citation

Pike CM, Theriot CM. Mechanisms of Colonization Resistance Against Clostridioides difficile. J Infect Dis. 2021 Jun 16;223(12 Suppl 2):S194-S200. doi: 10.1093/infdis/jiaa408. — View Citation

van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;3 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0	The severity of AE was graded as mild (grade 1), moderate (grade 2), severe/disabling (grade 3), life threatening (grade 4), and death (grade 5). All AE were divided in definitely, probably and possibly related to treatment. The treatment-related AE we focused on included microbiota-related AEs (e.g., infection, diarrhea, abdominal pain, etc.) and route of delivery related AEs (e.g., nausea, vomiting, etc.).	Four-week post-WMT
Secondary	The complete response rate of CDI-related diarrhea	The complete response of CDI-related diarrhea was defined as there was no diarrhea (1-2 times/day) for at least two consecutive days (normal stool characteristics (Bristol score =5) after treatment.	Four-week post-WMT,eight-week post-WMT
Secondary	Recurrence rate of CDI-related diarrhea.	Recurrence was defined as the CDI-related diarrhea reappeared, and the Clostridium difficile toxin test was positive after achieving complete response.	Four-week post-WMT,eight-week post-WMT
Secondary	Rate of major disease progression in CDI.	Disease progression refers to the worsening of symptoms associated with CDI, including increased diarrhea, toxic megacolon, organ failure, the need for emergency colectomy, and even death.	One-week post-WMT,Two-week post-WMT
Secondary	The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0	The severity of AE was graded as mild (grade 1), moderate (grade 2), severe/disabling (grade 3), life threatening (grade 4), and death (grade 5). All AE were divided in definitely, probably and possibly related to treatment. The treatment-related AE we focused on included microbiota-related AEs (e.g., infection, diarrhea, abdominal pain, etc.) and route of delivery related AEs (e.g., nausea, vomiting, etc.).	Eight-week post-WMT,six-month-post-WMT