Please select the eligibility criteria that correspond to the clinical trial below.
Title: Fecal Microbiota Transplant (FMT) for Relapsing C. Difficile Infection in Adults and Children Using a Frozen Inoculum
Brief Summary: Fecal microbiota transplantation (FMT) is the reconstitution of normal flora by a "stool transplant" from a healthy individual to a C. difficile-infected recipient, and has long been a successful approach to recurrent/refractory C. difficile. The purpose of this project is to generate a frozen FMT inoculum from well-screened healthy volunteer donors which can be used repeatedly, particularly in those who do not have a healthy intimate partner or other related donor. Delivery of FMT has been performed colonoscopically, by fecal retention enema, or by the nasogastric route. This study will evaluate the safety and secondarily the efficacy of a frozen inoculum administered by nasogastric tube vs administered by colonoscope.

Subjects with recurrent/relapsing C. difficile infection (10 per group) will receive FMT via either:

* colonoscopy
* NGT

The primary endpoint is assessment of safety as measured by clinical events (GI, procedural, systemic). Efficacy will be defined as a resolution of diarrhea off antibiotics for C. difficile, in the absence of a need for OTHER systemic antibiotics, i.e. resumption of a normal bowel status for the individual. Secondary efficacy endpoints include weight, subjective well-being and relative clinical improvement per standardized questionnaire, and subject qualitative assessment of, and satisfaction with, the transplant procedures. Subjects will be monitored for clinical safety by history and standard exams and the follow-up questionnaire as well as followed closely by phone and in person.


Options:
A: Inclusion Criteria:

* Male and female subjects 18 years of age or older
* Sexually active female subjects of child-bearing potential must agree to use an effective method of birth control during the treatment and follow-up period
* Required to sign an informed consent form
* Subject"s attending physician agrees to provide care following FMT
* Able to follow study procedures and follow-ups.
* Diagnosed by medical history of ≥ 3 RCDAD bouts in outpatients or ≥ 2 bouts of RCDAD in an inpatient with ≥ 2 positive fecal tests for C. difficile toxin
* Received at least one course of adequate antibiotic therapy for CDAD (≥ 10 days of vancomycin, metronidazole or fidaxomicin) after the subjects last bout of CDAD

Exclusion Criteria:

* Subjects with known neutropenia with absolute neutrophil count \<0.5 x 109/L
* Evidence of toxic megacolon, fulminant colitis, gastrointestinal perforation, ileus, abdominal distension, lack of bowel sounds, fever, or hypotension
* Known peripheral white blood cell count \> 15.0 x 109/L or temperature \> 38.0 °C
* Diarrhea due to definable non-CDAD pathogen
* Post total colectomy or presence of a colostomy
* Unable to tolerate FMT via enema for any reason
* Requiring systemic non-C. difficile antibiotic therapy at the time of FMT
* Actively taking Saccharomyces boulardii or other probiotic at the time of FMT
* Need for continuing use of oral vancomycin, oral or IV metronidazole, fidaxomicin, rifaximin or nitazoxanide at the time of FMT
* Severe underlying disease such that the patient is not expected to survive for one or more years or unstable medical condition requiring daily change in treatments
B: Patient inclusion criteria

1. Age 18 years or older.
2. Able to provide informed consent.
3. Laboratory or pathology: confirmed diagnosis of recurrent CDI with symptoms (defined below) within the previous 180 days.
4. ≥ 2 episodes of CDI within 6 months and/or ongoing symptoms consistent with CDI despite treatment with oral vancomycin at a dose of at least 125 mg 4 times daily for at least 5 days.

Symptoms of CDI, diarrhea deﬁned as: 3 or more unformed bowel movements in 24 hours for a minimum of 2 days with no other causes for diarrhea. Subjects will be required to have laboratory or pathology-confirmed diagnosis of recurrent C. difficile infection where recurrence is deﬁned as return of diarrhea and positive stool test after a period of symptom resolution within 8 weeks of the first episode and has received at least a 10-day course of standard antibiotic therapy.

Patient exclusion criteria

1. Planned or actively participating in another clinical trial.
2. Patients with neutropenia with absolute neutrophil count \<0.5 x 109/L
3. Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray
4. Peripheral white blood cell count \> 30.0 x 10E9/L AND temperature \> 38.0 oC
5. Active gastroenteritis due to Salmonella, Shigella, E. coli 0157H7, Yersinia or Campylobacter.
6. Presence of colostomy
7. Unable to tolerate HBT or enema for any reason.
8. Requiring systemic antibiotic therapy for more than 7 days.
9. Actively taking Saccharomyces boulardii
10. Severe underlying disease such that the patient is not expected to survive for at least 30 days.
11. Any condition that, in the opinion of the investigator, that the treatment may pose a health risk to the subject.

Donor inclusion

1. Able to provide and sign informed consent.
2. Able to complete and sign the donor questionnaire
3. Able to adhere to fecal transplantation stool collection standard operating procedure.

Donor exclusion

1. Tested positive for any of the following: Human Immunodeficiency virus (HIV) 1/2, hepatitis IgM, hepatitis B (HBsAg), hepatitis C antibody, syphilis, human T- lymphotrophic virus (HTLV) 1/II and vancomycin resistant Enterococcus (VRE), methicillin resistant S. aureus (MRSA), Salmonella, Shigella, E.coli O157 H7, Yersinia and Campylobacter.
2. Detection of ova, parasites, C. difficile toxin, norovirus, adenovirus, rotavirus on stool examination
3. History of any type of active cancer or autoimmune disease
4. History of risk factors for acquisition of HIV, syphilis, Hepatitis B, Hepatitis C, prion or any neurological disease as determined by the donor questionnaire, appendix B.
5. History of gastrointestinal comorbidities, e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation or diarrhea
6. Receipt of blood transfusion from a country other than Canada in preceding 6 months
7. Antibiotic use or any systemic immunosuppressive agents in the 3 months prior to stool donation
8. Receipt of any type of live vaccine within 3 months prior to stool donation
9. Ingestion of nut or shell fish 3 days preceding donation if the recipient has known allergies to these food.
10. Any current or previous medical or psychosocial condition or behaviours which in the opinion of the investigator may pose risk to the recipients or the donor
C: Inclusion Criteria:

1. Age \> 18 and \< 90 years at the time of Screening.
2. Diagnosis of at least 3 episodes of recurrent CDI, with each episode defined as presence of diarrhea (\> 3 unformed stools/24 hours) associate with positive stool Clostridium difficle toxin, occurring within 3 months of each other.
3. CDI infection under symptomatic control with \< 3 loose/unformed BM's per 24 h period for at least 2 consecutive days before procedure.
4. Those with ability to provide informed consent.

Exclusion Criteria:

1. Those with complicated CDI, defined as white blood cell\>35 or \<0.5 x 109/L, significant abdominal pain and distension with evidence of toxic megacolon or pseudomembranous colitis, hypotension defined as systolic blood pressure \< 90 mmHg unresponsive to fluid resuscitation, end organ failure, or requiring intensive care unit admission.
2. Those with chronic diarrheal illness, such as irritable bowel syndrome or inflammatory bowel disease unless they are in remission for at least 3 months prior to enrollment.
D: Inclusion Criteria:

* Patients with recurrent or relapsing CDI defined as EITHER(13):

  * At least three episodes of mild-to-moderate CDI and failure of a 6-8 week taper with vancomycin with or without an alternative antibiotic (e.g. rifaximin, nitazoxanide).
  * At least two episodes of severe CDI resulting in hospitalization and associated with significant morbidity.
* Willingness to accept risk of unrelated donor stool
* Willingness to be randomized to NGT vs. colonoscopic delivery.
* Able to consent for self, or parental assent/child assent as age appropriate.

Exclusion Criteria:

* Anatomic contraindication to NGT
* Delayed gastric emptying syndrome
* Known chronic aspiration
* Contraindication to colonoscopy (ASA 4 or more)
* High risk of bacterial translocation (Immunosuppression, cirrhosis etc)
* Pregnant or breastfeeding women
* Acute unrelated infection or comorbid illness exaccerbation

Answer: D