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Fresh, Frozen or Lyophilized Fecal Microbiota Transplantation for Multiple Recurrent C. Difficile Associated Diarrhea

Primary Purpose

Recurrent C. Difficile Associated Diarrhea

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Fecal Microbiota

About this trial

This is an interventional treatment trial for Recurrent C. Difficile Associated Diarrhea

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University of Texas Health Science Center at Housotn

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Fecal Microbiota_Fresh

Fecal Microbiota_Frozen

Fecal Microbiota_Lyophilized

Arm Description

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).

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 identity (ID) and expiration date which was 6 months after preparation day (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 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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

Full Information

NCT ID

NCT02318992

First Posted

December 9, 2014

Last Updated

April 19, 2019

Sponsor

The University of Texas Health Science Center, Houston

1. Study Identification

Unique Protocol Identification Number

NCT02318992

Brief Title

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

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

August 2013 (Actual)

Primary Completion Date

April 2018 (Actual)

Study Completion Date

April 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center, Houston

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent C. Difficile Associated Diarrhea

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

79 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fecal Microbiota_Fresh

Arm Type

Active Comparator

Arm Description

Arm Title

Fecal Microbiota_Frozen

Arm Type

Active Comparator

Arm Description

Arm Title

Fecal Microbiota_Lyophilized

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Fecal Microbiota

Intervention Description

Fecal Microbiota will be delivered via colonoscopy.

Primary Outcome Measure Information:

Title

Description

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

Secondary Outcome Measure Information:

Title

Number of Participants Who Had a Subsequent Bout of C-diff Associated Diarrhea

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Herbert L DuPont, MD

Organizational Affiliation

The University of Texas Health Science Center, Houston

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Zhi-Dong Jiang, MD, Dr.PH

Organizational Affiliation

The University of Texas Health Science Center, Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas Health Science Center at Housotn

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23223589

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.

Results Reference

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Citation

Mattila E, Uusitalo-Seppala R, Wuorela M, Lehtola L, Nurmi H, Ristikankare M, Moilanen V, Salminen K, Seppala M, Mattila PS, Anttila VJ, Arkkila P. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology. 2012 Mar;142(3):490-6. doi: 10.1053/j.gastro.2011.11.037. Epub 2011 Dec 7.

Results Reference

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PubMed Identifier

22290405

Citation

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Results Reference

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PubMed Identifier

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Citation

Brandt LJ. Fecal transplantation for the treatment of Clostridium difficile infection. Gastroenterol Hepatol (N Y). 2012 Mar;8(3):191-4. No abstract available.

Results Reference

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PubMed Identifier

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Citation

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PubMed Identifier

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Citation

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Citation

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Fresh, Frozen or Lyophilized Fecal Microbiota Transplantation for Multiple Recurrent C. Difficile Associated Diarrhea

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