Clinical trial NCT06106698: Washed Microbiota Transplantation for Clostridioides Difficile Infection
Official title: Washed Microbiota Transplantation for Clostridioides Difficile Infection: a Real World Research
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Clostridioides Difficile Infection
Keywords: washed microbiota transplantation
Clostridioides Difficile Infection
Intestinal infection
Antibiotic-associated Diarrhea
Lead sponsor: The Second Hospital of Nanjing Medical University
Sponsor class: OTHER
First posted: 2023-10-30
Enrollment: 100
Sex: ALL
Minimum age (years): 3
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: National patients with CDI receiving WMT will be enrolled.

Brief 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）.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0
timeFrame: Four-week post-WMT
Secondary outcomes:
measure: The complete response rate of CDI-related diarrhea
timeFrame: Four-week post-WMT，eight-week post-WMT
measure: Recurrence rate of CDI-related diarrhea.
timeFrame: Four-week post-WMT，eight-week post-WMT
measure: Rate of major disease progression in CDI.
timeFrame: One-week post-WMT，Two-week post-WMT
measure: The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0
timeFrame: Eight-week post-WMT，six-month-post-WMT
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The second affiliated hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The Second Hospital of Nanjing Medical University
name: Faming Zhang
role: PRINCIPAL_INVESTIGATOR
References:
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.S. Burden of Clostridioides difficile Infection and Outcomes. N Engl J Med. 2020 Apr 2;382(14):1320-1330. doi: 10.1056/NEJMoa1910215.
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. Epub 2013 Jun 26.
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.
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: 10.14309/ajg.0000000000001529. No abstract available.
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.
citation: 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.
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, Terveer EM, Nieuwdorp M, Lopez-Sanroman A, Kupcinskas J, Hart A, Tilg H, Gasbarrini A. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019 Dec;68(12):2111-2121. doi: 10.1136/gutjnl-2019-319548. Epub 2019 Sep 28.
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 Gastroenterology (APAGE) and Asia-Pacific Society for Digestive Endoscopy (APSDE). Gut. 2020 Jan;69(1):83-91. doi: 10.1136/gutjnl-2019-319407. Epub 2019 Oct 14.
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;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.