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: Participant Inclusion Criteria:

1. Children ages \>7 and ≤21 years of age with established diagnosis of Inflammatory Bowel Disease (IBD) colitis (patient with ulcerative colitis (UC) or patients with crohn's disease (CD) with colonic involvement only)
2. Have clinical disease (mild to moderate disease: 10≤ Pediatric Ulcerative Colitis Activity Index (PUCAI) \<65)
3. Have stable disease activity and therapy for two months prior to Gut Microbial Transplantation (GMT) procedure.

Participant Exclusion Criteria:

1. Fulminant colitis
2. Indication or scheduled for surgery
3. Pregnancy
4. Use of probiotic supplements during the study period (subjects who have stopped use of probiotic supplements will be eligible as long as they stop taking it 2 weeks prior to Day 1 of GMT)
5. anemia (hemoglobin \< 6.0 g/dL) in last one month
6. Graft versus host disease (GVHD)
7. Severely immunocompromised - defined as

   1. History of opportunistic infection (tuberculosis, Pneumocystis jirovecii or systemic fungal infections) in last one year or
   2. Neutropenia: Absolute neutrophil count (ANC) \<500
8. Major intra-abdominal surgery within 90 days prior to Day 1 of GMT
9. Administration of any investigational drug within 30 days prior to Day 1 of GMT.
10. Have received infliximab or other tumor necrosis factor (TNF) inhibitors within 2 months prior to Day 1 of GMT or are expected to receive such therapy within 1 month post final GMT.

Donor Inclusion Criteria

1. Based on patient's and parents'/guardian's decision
2. Will be chosen from immediate adult (≥18 years) family members or close friends
3. Should have negative or normal results on screening tests (as explained in donor exclusion criteria below)

Donor Exclusion Criteria (adopted from guidelines provided by American Association of Blood Bank Donor History Questionnaire and American Gastroenterological Association)

1. Positive or abnormal screening test to include:

   1. Hepatitis A Immunoglobulin M (IgM) antibody
   2. Hepatitis B antibody panel suggestive of infection (HBc IgM, HBs Ag, HBs Ab)
   3. Hepatitis C antibody Level
   4. Cytomegalovirus (CMV) IgM antibody
   5. Ebstein Barr Virus (EBV) viral capsid antigen (VCA) IgM antibody
   6. Syphilis Immunoglobulin G (IgG) Ab Screen
   7. Human Immune Deficiency Virus (HIV) I \& II enzyme-linked immunosorbent assay (ELISA) screen
   8. Stool i) Fungal smear ii) Stool cultures to exclude Salmonella, Shigella, Escherichia Coli, Campylobacter, Yersinia, Vibrio, Listeria iii) Clostridium difficile toxin assay iv) Ova and parasite screen for Giardia and Cryptosporidium
2. History of metabolic syndrome or gastric bypass surgery
3. History of GI conditions: IBD, irritable bowel syndrome, chronic abdominal pain, GI Malignancy, blood in stool or diarrhea in the last 4 weeks before enrollment
4. Antibiotic or probiotic use within 3 months before enrollment and for the duration of the donation
5. Positive response on screening questionnaire to any of the following:

   1. History of active malignancy or any cancer within the last 5 years (excluding basal cell carcinoma of the skin)
   2. Family history of Creutzfeld-Jacob disease
   3. Corneal or dural transplant
   4. History of high risk sexual behavior (e.g. sexual contact with HIV/acquired immune deficiency syndrome (AIDS) positive, hepatitis positive partner, men who have sex with men, sex for drugs or money)
   5. History of signs of sexually transmitted infections such as genital ulcerations, anogenital herpes, anogenital warts, cancroids or syphilitic lesions
   6. Use of illicit drugs
   7. Travel within the last 6 months to areas of the world where diarrheal illnesses are endemic
   8. History or signs of immunosuppression i) History of any immunosuppressant medication(s) within the last 6 months or history of opportunistic infection(s) in past 1 year ii) Signs of immunosuppression such as:

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   1. Oral thrush
   2. Disseminated lymphadenopathy
B: Inclusion Criteria:

1. Adult outpatients (age ≥18 and \<75) referred to one of the study centers after suffering a third (or further) documented episode CDI and
2. who have failed to maintain CDI cure after standard therapy with oral vancomycin.

   * Previous treatment with at least one course of tapered/pulse dose vancomycin as per SHEA-IDSA C difficile treatment guidelines or -Inability to taper or stop vancomycin without developing diarrhea requiring anti-infective therapy. -

Exclusion Criteria:

* Patients who are aged 75 years or greater.
* Patients who are pregnant
* Patients who are nursing
* Patients who are incarcerated
* Patients with cognitive impairment or severe neuropsychiatric co morbidities who are incapable of giving their own informed consent
* Patients who are immunocompromised specifically:
* HIV infection (any CD4 count)
* AIDS-defining diagnosis or CD4\<200/mm3
* Inherited/primary immune disorders
* Immunodeficient or Immunosuppressed due to medical condition/medication:
* Current or recent (\<3 most) treatment with anti-neoplastic agent
* Current or recent (\<3 mos) treatment with any immunosuppressant medications (including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil). Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.
* Patients with a history of severe (anaphylactic) food allergy
* Patients who have previously undergone FMT
* Patients who are unwilling or unable to undergo colonoscopy
* Patients with untreated, in-situ colorectal cancer
* Patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn"s disease or microscopic colitis) or irritable bowel syndrome
* Unable to comply with protocol requirements
* Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V
* Patients with acute illness or fever on the day of planned FMT will be excluded (not undergo randomization or treatment with FMT) with the option of including that subject at a future date.
C: 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
D: Inclusion Criteria:

* 3yo to 17yo at start of trial
* Followed at a participating clinical trial site: a) McMaster Children's Hospital, b) Children's Hospital at London Health Sciences Centre, c) Centre Hospitalier Universitaire Sainte-Justine
* Ulcerative colitis (UC) or Inflammatory bowel disease unclassified (IBD-U)
* Evidence of active clinical, biological, or mucosal disease
* Ongoing treatment is acceptable provided the patient has had no significant changes to medications, or medication dose for at least 4 weeks prior to starting the trial

Exclusion Criteria:

* Active participation in another therapeutic trial
* Unable to give informed consent, or assent
* Active Clostridium difficile infection
* Significant change in medication type, or medication dose within the preceding 4 weeks prior to starting the trial
* Starting new treatments, or having a significant change in medication dosing during the trial
* Significant, consecutive rise in PUCAI score during the trial
* Hospitalization during trial

Answer: C