Clinical trial NCT02318992: Fresh, Frozen or Lyophilized Fecal Microbiota Transplantation for Multiple Recurrent C. Difficile Associated Diarrhea
Official title: Fresh, Frozen or Lyophilized Fecal Microbiota Transplantation for Multiple Recurrent C. Difficile Associated Diarrhea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent C. Difficile Associated Diarrhea
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2014-12-18
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to investigate the efficacy of fresh, frozen or lyophilized fecal microbiota transplantation (FMT) via colonoscopy in patients with recurrent C. difficile associated diarrhea (RCDAD). Frozen, lyophilized or fresh fecal microbiota transplantation (FMT) inoculum will be generated from well-screened healthy volunteer donors of ≥150 gram/sample. Delivery of FMT will be performed colonoscopically. Fecal samples from donors and recipients will be saved for later metagenomic studies to characterize the microbiome of the gut in patients before and after FMT.


Eligibility criteria: Inclusion Criteria:

Recipients

* Male and female patients ≥ 18 years of age
* Sexually active male and female patients of child-bearing potential must agree to use an effective method of birth control during the treatment and follow-up period
* Female patients of child-bearing potential must have a negative pregnancy test in the 72 hours before the procedure
* Required to sign an informed consent form
* Deemed likely to survive for ≥ 3 months after enrolment
* Diagnosis of ≥ 3 recurrent CDAD (RCDAD) bouts in outpatients or ≥ 2 bouts of CDAD in an inpatient without other explanation for diarrhea and with ≥ 2 positive fecal tests for C. difficile toxin
* Referred by subjects attending physician who will provide non-transplant care for the subject and follow up at 1, 7, 14, 30 days after FMT
* Received at least one course of adequate antibiotic therapy for CDAD (≥ 10 days of vancomycin at a dose of ≥125 mg four times per day, ≥ 10 days of metronidazole at a dose of 500mg three times per day or fidaxomixin 200mg twice a day for 10 days
* Anti-Clostridium difficile infection (CDI) antibiotic treatment stopped 2-4 days before the transplantation

Donors

* Able to provide and sign informed consent
* Able to complete and sign the donor questionnaire
* Able to adhere to fecal transplantation stool collection requirements

Exclusion Criteria:

Recipients

* Patients with neutropenia with absolute neutrophil count \<0.5 x 109/L
* Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray
* Peripheral white blood cell count \> 15.0 x 109/L AND temperature \> 38.0 °C
* Active gastroenteritis due to Salmonella, Shigella, E. coli 0157:H7, Yersinia or Campylobacter, and Norovirus
* Presence of colostomy
* Unable to tolerate human biotherapy (HBT) for any reason
* Requiring systemic antibiotic therapy for more than 7 days
* Actively taking Saccharomyces boulardii or other probiotic
* 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
* Prolonged compromised immunity due to cytotoxic chemotherapy or HIV infection

Donors

* Test positive for any of variables
* History of any type of active cancer or autoimmune disease
* History of risk factors for acquisition of HIV, syphilis, Hepatitis B, Hepatitis C, prion or any neurological disease as determined by the donor questionnaire
* History of gastrointestinal disorder, e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation or diarrhea
* Antibiotic use or any systemic immunosuppressive agents in the 3 months prior to stool donation
* Receipt of any type of live vaccine within 3 months prior to stool donation
* Current or previous medical or psychosocial condition
* Body mass index over 30

Primary outcomes:
measure: Safety of Fresh, Frozen or Lyophilized Intestinal Bacteria From Healthy Donors Given by Colonoscopy for Therapy in Subjects With Recurrent C. Difficile Associated Diarrhea (RCDAD) as Assessed by Number of Participants Who Any Adverse Event
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants Who Had a Subsequent Bout of C-diff Associated Diarrhea
timeFrame: 30 days
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas Health Science Center at Housotn
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Herbert L DuPont, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center, Houston
name: Zhi-Dong Jiang, MD, Dr.PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jiang ZD, Hoang LN, Lasco TM, Garey KW, Dupont HL. Physician attitudes toward the use of fecal transplantation for recurrent Clostridium difficile infection in a metropolitan area. Clin Infect Dis. 2013 Apr;56(7):1059-60. doi: 10.1093/cid/cis1025. Epub 2012 Dec 7. No abstract available.
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