Recurrent C. Difficile Associated Diarrhea
Conditions
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.
Interventions
BIOLOGICALFecal Microbiota
Fecal Microbiota will be delivered via colonoscopy.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 months | Any untoward medical occurrence associated with the use of PRIM-DJ2727 whether or not considered drug related is considered as an adverse event (AE) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had a Subsequent Bout of C-diff Associated Diarrhea | 30 days | a subsequent bout of C-diff associated diarrhea was defined as diarrhea, C. difficile toxins positive and using anti-C. difficile antibiotic treatment |
Countries
United States
Participant flow
Pre-assignment details
79 were enrolled; however only 78 started--this is because one person who enrolled withdrew before treatment initiation due to insurance problem.
Participants by arm
| Arm | Count |
|---|---|
| Fecal Microbiota_Fresh Donor stool (greater than 150 grams) was collected \<4 hours prior to the procedure and then mixed in a homogenizer with 1500 milliliters (mL) (1:10 dilution) sterilized 0.9% sodium chloride (NaCl) in a large sterilized suction canister until a smooth consistency was reached. The suspension was filtered using a coffee filter twice. The microbiota suspension (250mL) was used within 2 hours of preparation (Fresh).
Fecal Microbiota: Fecal Microbiota will be delivered via colonoscopy. | 27 |
| Fecal Microbiota_Frozen Donor stool (greater than 150 grams) was collected \<4 hours prior to the procedure and then mixed in a homogenizer with 1500 milliliters (mL) (1:10 dilution) sterilized 0.9% NaCl in a large sterilized suction canister until a smooth consistency was reached. The suspension was filtered using a coffee filter twice. The microbiota suspension (250mL) was kept at -80 degrees celsius (C) freezer labeled with ID and expiration date which was 6 months after preparation day (Frozen).
Fecal Microbiota: Fecal Microbiota will be delivered via colonoscopy. | 27 |
| Fecal Microbiota_Lyophilized Donor stool (greater than 150 grams) was collected \<4 hours prior to the procedure and then mixed in a homogenizer with 1500 milliliters (mL) (1:10 dilution) sterilized 0.9% NaCl in a large sterilized suction canister until a smooth consistency was reached. The suspension was filtered using a coffee filter twice. The microbiota suspension (250mL) was starting lyophilization process within 30 minutes after completion of stool filtration (Lyophilized). Lyophilized microbiota products were kept at 4 degrees celsius (C) and were used within 6 months after preparation day.
Fecal Microbiota: Fecal Microbiota will be delivered via colonoscopy. | 24 |
| Total | 78 |
Baseline characteristics
| Characteristic | Fecal Microbiota_Fresh | Fecal Microbiota_Frozen | Fecal Microbiota_Lyophilized | Total |
|---|---|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 20.04 | 63 years STANDARD_DEVIATION 13.79 | 59 years STANDARD_DEVIATION 19.27 | 63 years STANDARD_DEVIATION 17.9 |
| duration since last Clostridium difficile infection (CDI) bout in 0.5 month increments | 2 half months STANDARD_DEVIATION 2.06 | 2 half months STANDARD_DEVIATION 1.97 | 2 half months STANDARD_DEVIATION 1.36 | 2 half months STANDARD_DEVIATION 1.8 |
| Number of Patients used Anti-C. difficile infection (CDI) treatment 6 months before the procedure | 25 Participants | 24 Participants | 24 Participants | 73 Participants |
| Number of Patients with Crohn's Disease | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Number of Patients with Inflammatory bowel disease | 7 Participants | 4 Participants | 5 Participants | 16 Participants |
| Number of Patients with Ulcerative Colitis | 6 Participants | 3 Participants | 3 Participants | 12 Participants |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment United States | 27 Participants | 27 Participants | 24 Participants | 78 Participants |
| Sex: Female, Male Female | 21 Participants | 18 Participants | 13 Participants | 52 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 11 Participants | 26 Participants |
| total number Clostridium difficile infection (CDI) bouts before fecal microbiota transplantation | 4 counts STANDARD_DEVIATION 0.87 | 4 counts STANDARD_DEVIATION 0.93 | 4 counts STANDARD_DEVIATION 2.24 | 4 counts STANDARD_DEVIATION 1.35 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 1 / 27 | 0 / 24 |
| other Total, other adverse events | 2 / 26 | 2 / 27 | 6 / 24 |
| serious Total, serious adverse events | 0 / 26 | 1 / 27 | 1 / 24 |
Outcome results
Primary
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
Any untoward medical occurrence associated with the use of PRIM-DJ2727 whether or not considered drug related is considered as an adverse event (AE)
Time frame: 6 months
Population: One subject in the Fecal Microbiota\_Fresh group was lost to follow up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Microbiota_Fresh | 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 | 15 Participants |
| Fecal Microbiota_Frozen | 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 | 23 Participants |
| Fecal Microbiota_Lyophilized | 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 | 17 Participants |
p-value: 0.157Chi-squared, Corrected
Secondary
Number of Participants Who Had a Subsequent Bout of C-diff Associated Diarrhea
a subsequent bout of C-diff associated diarrhea was defined as diarrhea, C. difficile toxins positive and using anti-C. difficile antibiotic treatment
Time frame: 30 days
Population: One subject in the Fecal Microbiota\_Fresh group was lost to follow up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Microbiota_Fresh | Number of Participants Who Had a Subsequent Bout of C-diff Associated Diarrhea | 1 Participants |
| Fecal Microbiota_Frozen | Number of Participants Who Had a Subsequent Bout of C-diff Associated Diarrhea | 3 Participants |
| Fecal Microbiota_Lyophilized | Number of Participants Who Had a Subsequent Bout of C-diff Associated Diarrhea | 7 Participants |
p-value: 0.041Chi-squared, Corrected