Clinical trial NCT01973465: Fecal Microbiota Therapy for Recurrent Clostridium Difficile Colitis
Official title: Fecal Microbiota Therapy for Recurrent Clostridium Difficile Colitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Clostridium Difficile
Keywords: C-Diff
Diarrhea
Lead sponsor: OSF Healthcare System
Sponsor class: OTHER
First posted: 2013-10-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study was developed in response to the July, 2013 FDA draft guidance regarding FMT for CDI. The weight of the evidence in the literature suggests that FMT is the most effective treatment for ambulatory outpatients affected by recurrent CDI who fail conventional therapy.

The anticipated benefits to research patients enrolled in this study include resolution of chronic diarrhea, return of bowel habits and nutritional status to normal, and resolution of chronic recurrent CDI.

FMT involves the endoscopic instillation of freshly obtained stool with millions of live bacteria into the recipient's colon by endoscopic lavage. With any endoscopic procedure, there is a risk of perforated viscous. This is very rare, but the risk is increased with severe CDI. The risk of acquisition of communicable enteric or blood borne pathogen appears to be negligible.


Eligibility criteria: Inclusion Criteria:

1. Patients \> 18 years of age
2. The patient has been treated with appropriate antimicrobial therapy for CDI.
3. The patient has documented relapse/recurrence of infection as demonstrated by positive stool culture, or cytotoxin assay, or PCR toxin assay.
4. Since this study does not involve treatments that have potential teratogenicity, and in general avoidance of antimicrobial treatment during pregnancy is advised (metronidazole is pregnancy category C), women of child-bearing age may be included in the study.

Exclusion Criteria:

- Patients will be excluded from study participation if one of the following categories of exclusion criteria applies:

1. Patient is \< 18 years of age
2. Patient has an absolute neutrophil count \< 750 cells/mm3.

Stool donors must:

1. be \> 18 years of age
2. Complete a screening questionnaire:

   a. One-time donors: Table 1 b. Designated, pre-screened donors: Table 2
3. Be tested for communicable blood-borne and enteric pathogens:

   1. One-time donors: Table 3
   2. Designated, pre-screened donors: Table 4

Table 1: Questionnaire to screen one-time stool donors prior to FMT.

You have been identified as a potential stool donor by __________________ , your (spouse/ son/ daughter/ mother/ father/ life partner), who has been referred for fecal transplantation. Prior to performing the transplantation procedure, the OSF/Saint Francis Medical Center Infection Control Committee requires completion of a screening questionnaire by all potential stool donors:

Your name: ___________________________________________ Date: ___/___/ 2013

Your relationship to the patient: ___________________________ YES / NO

1. Have you ever been diagnosed with Clostridium difficile colitis?
2. Are you currently taking antibiotic medications?
3. Have you been prescribed antibiotics in the past six weeks?

IF the potential stool donor answers YES to questions 1, 2, or 3 - please STOP.

Do you have a history of any of the following: (Please Circle)

Hepatitis A YES / NO Hemophilia YES / NO Hemodialysis treatment YES / NO Rejected or refused blood donation YES / NO HIV/AIDS YES / NO Hepatitis B YES / NO Hepatitis C YES / NO Use of intravenous drugs or medications YES / NO Incarceration YES / NO Abnormal blood tests of liver enzymes YES / NO Accepting money or drugs in exchange for sex YES / NO Receipt of a blood transfusion between 1977 - 1992 YES / NO Infectious gastroenteritis or diarrhea YES / NO

Did you answer YES to any of the above? YES / NO

Table 2: Questionnaire to screen designated stool donors prior to each FMT.

You have been identified as a potential stool donor for a patient who has been referred to Saint Francis Medical Center for fecal transplantation. Prior to performing the transplantation procedure, the OSF/Saint Francis Medical Center Infection Control Committee requires completion of a screening questionnaire by all potential stool donors:

Your name: ___________________________________________ Date: ___/___/ 2013

Your relationship to the patient: ___________________________ YES / NO

1. Have you ever been diagnosed with Clostridium difficile colitis?

4. Are you currently taking antibiotic medications?

5. Have you been prescribed antibiotics in the past six weeks?

IF the potential stool donor answers YES to questions 1, 2, or 3 - please STOP.

Do you have a history of any of the following: (Please Circle)

Hepatitis A YES / NO Hemophilia YES / NO Hemodialysis treatment YES / NO Rejected or refused blood donation YES / NO HIV/AIDS YES / NO Hepatitis B YES / NO Hepatitis C YES / NO Use of intravenous drugs or medications YES / NO Incarceration YES / NO Abnormal blood tests of liver enzymes YES / NO Accepting money or drugs in exchange for sex YES / NO Receipt of a blood transfusion between 1977 - 1992 YES / NO Infectious gastroenteritis or diarrhea YES / NO

Did you answer YES to any of the above? YES / NO

Table 3: Required stool donor screening laboratory studies prior to FMT

Stool:

Giardia \& Cryptosporidium stool antigen testing Stool ova \& parasite testing Cultures for Salmonella, Shigella and E. coli O157:H7 Clostridium difficile toxin B PCR assay

Blood:

HIV 1\&2 Ab/Ag HAV IgM Ab HBV core Ab \& Ag HCV Ab HTLV-1 Ab

Table 4: Laboratory studies every 120 days for designated stool donors

Stool:

Giardia \& Cryptosporidium stool antigen testing Stool ova \& parasite testing Cultures for Salmonella, Shigella and E. coli O157:H7 Clostridium difficile toxin B PCR assay

Blood:

HIV 1\&2 Ab/Ag HAV IgM Ab HBV core Ab \& Ag HCV Ab HTLV-1 Ab

Primary outcomes:
measure: Weight and Number of bowel movements/day
timeFrame: 30 and 90 days
Secondary outcomes:
measure: Evaluate the most appropriate patient population for FMT
timeFrame: 30 and 90 days
measure: Determine the overall success of FMT
timeFrame: 30 and 90 days
Other outcomes:
Locations:
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
Study officials:
affiliation: OSF Healthcare System
name: John J Farrell, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hall IC, O'Toole E. Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, Bacillus difficilis. Am J Dis Child 1935;49:390-402.
citation: Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978 Mar 9;298(10):531-4. doi: 10.1056/NEJM197803092981003.
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.
citation: Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011 Nov;53(10):994-1002. doi: 10.1093/cid/cir632.
citation: True E, Tsoraides S, Bonello JP. Fecal Microbiota Therapy in the Treatment of Clostridium difficile diarrhea. 63rd Annual Scientific Meeting, Illinois Chapter, American College of Surgeons. June 7, 2013.
citation: Sax, PE. NEJM Journal Watch. http://blogs.jwatch.org/hiv-id-observations/index.php/fda-fecal- transplants-need-investigational-new-drug-application/2013/05/12/