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

NCT02318992 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HSC-SPH-13-0119
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent C. Difficile Associated Diarrhea

Outcome Measures

Primary Outcomes (1)

• 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)

  6 months

Secondary Outcomes (1)

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

  30 days

Study Arms (3)

Fecal Microbiota_Fresh

ACTIVE COMPARATOR

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).

Biological: Fecal Microbiota

Fecal Microbiota_Frozen

ACTIVE COMPARATOR

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).

Biological: Fecal Microbiota

Fecal Microbiota_Lyophilized

ACTIVE COMPARATOR

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.

Biological: Fecal Microbiota

Interventions

Fecal Microbiota BIOLOGICAL

Fecal Microbiota will be delivered via colonoscopy.

Fecal Microbiota_Fresh; Fecal Microbiota_Frozen; Fecal Microbiota_Lyophilized

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

University of Texas Health Science Center at Housotn

Houston, Texas, 77030, United States

Location

Related Publications (12)

• 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.

  PMID: 23223589 BACKGROUND

• 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.

  PMID: 22155369 BACKGROUND

• Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012 May;107(5):761-7. doi: 10.1038/ajg.2011.482. Epub 2012 Jan 31.

  PMID: 22290405 BACKGROUND

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

  PMID: 22675283 BACKGROUND

• Bakken JS, Borody T, Brandt LJ, Brill JV, Demarco DC, Franzos MA, Kelly C, Khoruts A, Louie T, Martinelli LP, Moore TA, Russell G, Surawicz C; Fecal Microbiota Transplantation Workgroup. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011 Dec;9(12):1044-9. doi: 10.1016/j.cgh.2011.08.014. Epub 2011 Aug 24.

  PMID: 21871249 BACKGROUND

• EISEMAN B, SILEN W, BASCOM GS, KAUVAR AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958 Nov;44(5):854-9. No abstract available.

  PMID: 13592638 BACKGROUND

• Brandt LJ, Reddy SS. Fecal microbiota transplantation for recurrent clostridium difficile infection. J Clin Gastroenterol. 2011 Nov;45 Suppl:S159-67. doi: 10.1097/MCG.0b013e318222e603.

  PMID: 21992957 BACKGROUND

• Borody TJ, Warren EF, Leis S, Surace R, Ashman O. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol. 2003 Jul;37(1):42-7. doi: 10.1097/00004836-200307000-00012.

  PMID: 12811208 BACKGROUND

• Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet. 1989 Jan 21;1(8630):164. doi: 10.1016/s0140-6736(89)91183-5. No abstract available.

  PMID: 2563083 BACKGROUND

• Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M, Gormley N, Gilbert JA, Smith G, Knight R. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012 Aug;6(8):1621-4. doi: 10.1038/ismej.2012.8. Epub 2012 Mar 8.

  PMID: 22402401 BACKGROUND

• Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010 Oct 1;26(19):2460-1. doi: 10.1093/bioinformatics/btq461. Epub 2010 Aug 12.

  PMID: 20709691 BACKGROUND

• Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010 May;7(5):335-6. doi: 10.1038/nmeth.f.303. Epub 2010 Apr 11. No abstract available.

  PMID: 20383131 BACKGROUND

MeSH Terms

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Limitations and Caveats

Microbiota analyses was not performed on the subjects with Fecal Microbiota Transplantation (FMT) failure who could not provide four stools. Microbiota was not studied at the species level. Limited sample size of the study.

Results Point of Contact

• Title: Dr. Herbert DuPont
• Organization: University of Texas School of Public Health

herbert.l.dupont@uth.tmc.edu

713 500 9366

Study Officials

• Herbert L DuPont, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Zhi-Dong Jiang, MD, Dr.PH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 9, 2014
• First Posted: December 18, 2014
• Study Start: August 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: May 23, 2024
• Results First Posted: May 13, 2019

Record last verified: 2024-05

Locations

US (1)