Recurrent C. Difficile Associated Diarrhea Clinical Trial
Official title:
Fresh, Frozen or Lyophilized Fecal Microbiota Transplantation for Multiple Recurrent C. Difficile Associated Diarrhea
| Verified date | May 2024 |
| Source | The University of Texas Health Science Center, Houston |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 79 |
| Est. completion date | April 2018 |
| Est. primary completion date | April 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Texas Health Science Center at Housotn | Houston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| The University of Texas Health Science Center, Houston |
United States,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View 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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View 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. — View 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. — View Citation
* Note: There are 12 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| 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) | 6 months | |
| 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 | 30 days |