Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Study of Fecal Microbiota Transplantation (FMT) for the Treatment of Recurrent C. Difficile Associated Diarrhea (RCDAD) Via Retention Enema or Oral Route
Brief Summary: The objective of the study is to investigate the safety of a frozen or lyophilized inoculum administered, respectively, by retention enema or capsules in patients with recurrent C. difficile associated diarrhea (RCDAD).

This is a single center, randomized, parallel assignment, open label safety study conducted in subjects with RCDAD. Fifty subjects will be enrolled in the study and randomized at 1:1 ratio to receive frozen filtered intestinal bacteria via retention enema or lyophilized donor intestinal bacteria. All subjects will be followed for a total of 3 years after study completion.

Donors will be enrolled and screened at the laboratory in the Center for Infectious Diseases at University of Texas School of Public Health (UT-SPH). The donors will come from a variety of places, including the UT-SPH. At least 20 donors will be screened to recruit at least 15 qualified donors.

Recipients may self-refer but must have a physician who agrees to accept care of the patient following fecal microbiota transplantation (FMT). Subjects consenting to treatment at Baylor St. Luke's Medical Center (BSLMC) and the UT-SPH must be willing to self-pay for the FMT in the amount of $1,500. There will be no insurance accepted. Subjects undergoing retention enema will be treated as outpatients at either at BSLMC, Kelsey-Seybold Clinic, or at the Memorial Hermann in the Texas Medical Center. All subjects taking capsules with lyophilized intestinal bacteria will be seen at UT-SPH. Once the procedure is completed, the recipient's care will be returned to their physician. At least 75 recipients will be screened to recruit 50 qualified recipients.

The primary endpoint is to evaluate the safety of FMT by rectal or oral routes with secondary endpoint related to efficacy prevention of RCDAD. In order to monitor any health effects for safety, participants will be contacted pre- and 7, 14, 30 days, then monthly basis for the first 90 days after FMT and quarterly till 3 years after FMT. The following procedures will be completed: review recipient diary with the recipient to ensure that the following information is recorded correctly and a fresh stool sample will be collected from recipient, tested for C. difficile toxins and an aliquot (2mL) stored at -80C for microbiome analysis. Recipients will be contacted by phone for their diarrhea status on monthly basis till 90 days after FMT, then on quarterly basis till 3 years after FMT.


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: Inclusion Criteria for patients:

* Patients with IBS-D according to Roma 3 criteria

Exclusion Criteria for patients:

* Immunomodulating medication
* Nocturnal abdominal pain
* Constant abdominal pain
* Alarm symptoms like rectal bleeding, weight loss, nightsweats
* Symptomatic heart/vascular/lung disease
* Renal failure
* Known food allergy
* Microscopic/collagenous colitis
* non-compliant
* BMI \<18

Inclusion criteria for donors:

* healthy volunteers

Exclusion criteria for donors

* Tattoos, imprisoning or piercing last 3 months
* Any history of chronic diarrhoea, constipation, inflammatory bowel disease, irritable bowel disease, colorectal polyps or cancer, immunosuppression, morbid obesity, metabolic syndrome, atopica, or fatigue
* positive test for hepatitis B, C, HIV, treponema pallidum
* sexual high risk habits
* antibiotic treatment in the past 3 months
C: Inclusion criteria:

* Recurrent C. difficile infection (identified by positivity of C. difficile toxin in stools) with severe clinical picture (defined by the ESCMID Guidelines published in 2014 - Debast et al, Clin Microbiol Infect 2014)
* Possibility to undergo standard antimicrobial therapy for recurrent C. difficile infection Approval of informed consent
* Possibility to undergo protocol diagnostic and therapeutic procedures
* Stool negativity for parasites
* Stool negativity for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms except for C. difficile
* Blood negativity for: Hepatitis A virus-Immunoglobulin M, HBsAg, Anti-Hepatitis C Virus, Anti-Human Immunodeficiency Virus1-2, venereal disease reaction level (VDRL).

Exclusion Criteria:

* Subjects \<18 years old
* Prior colectomy
* Negativity of C. difficile toxin in stools
* Mild clinical picture of C. difficile infection
* High risk of post-colonoscopy complications
* Other main gastrointestinal diseases (es. Crohn's disease or ulcerative colitis)
* Stool positivity for parasites
* Stool positivity for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms except for C. difficile
* Blood positivity for: Hepatitis A virus-Immunoglobulin M, HBsAg, Anti-Hepatitis C Virus, Anti-Human Immunodeficiency Virus1-2, venereal disease reaction level (VDRL).
* Pregnancy or breastfeeding.
* Inability to follow protocol procedures
D: 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.

Answer: A