Fecal Microbiota Transplantation to Treat Recurrent C. Difficile Associated Diarrhea Via Retention Enema or Oral Route

NCT02449174 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HSC-SPH-14-0020
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to investigate the safety of a frozen or lyophilized inoculum administered, respectively, by retention enema or capsules in patients with recurrent C. difficile associated diarrhea (RCDAD). This is a single center, randomized, parallel assignment, open label safety study conducted in subjects with RCDAD. Fifty subjects will be enrolled in the study and randomized at 1:1 ratio to receive frozen filtered intestinal bacteria via retention enema or lyophilized donor intestinal bacteria. All subjects will be followed for a total of 3 years after study completion. Donors will be enrolled and screened at the laboratory in the Center for Infectious Diseases at University of Texas School of Public Health (UT-SPH). The donors will come from a variety of places, including the UT-SPH. At least 20 donors will be screened to recruit at least 15 qualified donors. Recipients may self-refer but must have a physician who agrees to accept care of the patient following fecal microbiota transplantation (FMT). Subjects consenting to treatment at Baylor St. Luke's Medical Center (BSLMC) and the UT-SPH must be willing to self-pay for the FMT in the amount of $1,500. There will be no insurance accepted. Subjects undergoing retention enema will be treated as outpatients at either at BSLMC, Kelsey-Seybold Clinic, or at the Memorial Hermann in the Texas Medical Center. All subjects taking capsules with lyophilized intestinal bacteria will be seen at UT-SPH. Once the procedure is completed, the recipient's care will be returned to their physician. At least 75 recipients will be screened to recruit 50 qualified recipients. The primary endpoint is to evaluate the safety of FMT by rectal or oral routes with secondary endpoint related to efficacy prevention of RCDAD. In order to monitor any health effects for safety, participants will be contacted pre- and 7, 14, 30 days, then monthly basis for the first 90 days after FMT and quarterly till 3 years after FMT. The following procedures will be completed: review recipient diary with the recipient to ensure that the following information is recorded correctly and a fresh stool sample will be collected from recipient, tested for C. difficile toxins and an aliquot (2mL) stored at -80C for microbiome analysis. Recipients will be contacted by phone for their diarrhea status on monthly basis till 90 days after FMT, then on quarterly basis till 3 years after FMT.

Conditions

C. Difficile

Keywords

C. difficile; Fecal Microbiota transplantation

Outcome Measures

Primary Outcomes (1)

• Safety as Assessed by Number of Participants With Any Adverse Events (AE)s

  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 after the procedure

Secondary Outcomes (1)

• Number of Participants Who Continue to Have Diarrhea and C. Difficile Toxin Following Fecal Microbiota Transplantation From a Healthy Donor

  60 days after the procedure

Study Arms (2)

Frozen Microbiota

ACTIVE COMPARATOR

Donor stool (greater than 150 grams) was collected \<4 hours prior to the procedure and then mixed in a homogenizer with 750mL, 1:5 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 (750mL) was kept at -80C labeled with ID and expiration date which was 6 months after preparation. Intervention - Frozen Microbiota will be delivered via enema

Biological: Frozen Microbiota

Lyophilized Microbiota

ACTIVE COMPARATOR

Lyophilized Microbiota\_Donor stool (greater than 150 grams) was collected \<4 hours prior to the procedure and then mixed in a homogenizer with 750mL, 1:5 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 (750mL) was starting lyophilization process within 30 minutes after completion of stool filtration. Lyophilized microbiota products were kept at 4C and were used within 6 months after preparation. Intervention - Lyophilized Microbiota will be delivered orally

Biological: Lyophilized Microbiota

Interventions

Frozen Microbiota BIOLOGICAL

Frozen Microbiota will be delivered via enema route.

Frozen Microbiota

Lyophilized Microbiota BIOLOGICAL

Lyophilized Microbiota will be delivered orally.

Lyophilized Microbiota

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects 18 years of age or older
• Sexually active female subjects of child-bearing potential must agree to use an effective method of birth control during the treatment and follow-up period
• Required to sign an informed consent form
• Subject"s attending physician agrees to provide care following FMT
• Able to follow study procedures and follow-ups.
• Diagnosed by medical history of ≥ 3 RCDAD bouts in outpatients or ≥ 2 bouts of RCDAD in an inpatient with ≥ 2 positive fecal tests for C. difficile toxin
• Received at least one course of adequate antibiotic therapy for CDAD (≥ 10 days of vancomycin, metronidazole or fidaxomicin) after the subjects last bout of CDAD

You may not qualify if:

• Subjects with known neutropenia with absolute neutrophil count \<0.5 x 109/L
• Evidence of toxic megacolon, fulminant colitis, gastrointestinal perforation, ileus, abdominal distension, lack of bowel sounds, fever, or hypotension
• Known peripheral white blood cell count \> 15.0 x 109/L or temperature \> 38.0 °C
• Diarrhea due to definable non-CDAD pathogen
• Post total colectomy or presence of a colostomy
• Unable to tolerate FMT via enema for any reason
• Requiring systemic non-C. difficile antibiotic therapy at the time of FMT
• Actively taking Saccharomyces boulardii or other probiotic at the time of FMT
• Need for continuing use of oral vancomycin, oral or IV metronidazole, fidaxomicin, rifaximin or nitazoxanide at the time of FMT
• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Roderick MacDonald Research Fund at Baylor St. Luke's: collaborator
• Kelsey Research Foundation: collaborator
• Texas Gulf Coast Digestive Diseases Center: collaborator

Study Sites (1)

University of Texas Health Science Center at Housotn

Houston, Texas, 77030, United States

Location

Related Publications (10)

• Kelly CP, LaMont JT. Clostridium difficile--more difficult than ever. N Engl J Med. 2008 Oct 30;359(18):1932-40. doi: 10.1056/NEJMra0707500. No abstract available.

  PMID: 18971494 BACKGROUND

• Gravel D, Gardam M, Taylor G, Miller M, Simor A, McGeer A, Hutchinson J, Moore D, Kelly S, Mulvey M; Canadian Nosocomial Infection Surveillance Program. Infection control practices related to Clostridium difficile infection in acute care hospitals in Canada. Am J Infect Control. 2009 Feb;37(1):9-14. doi: 10.1016/j.ajic.2008.07.012.

  PMID: 19171246 BACKGROUND

• Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, Young VB. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008 Feb 1;197(3):435-8. doi: 10.1086/525047.

  PMID: 18199029 BACKGROUND

• Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet. 1989 May 27;1(8648):1156-60. doi: 10.1016/s0140-6736(89)92749-9.

  PMID: 2566734 BACKGROUND

• Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol. 2010 May-Jun;44(5):354-60. doi: 10.1097/MCG.0b013e3181c87e02.

  PMID: 20048681 BACKGROUND

• Yoon SS, Brandt LJ. Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients. J Clin Gastroenterol. 2010 Sep;44(8):562-6. doi: 10.1097/MCG.0b013e3181dac035.

  PMID: 20463588 BACKGROUND

• Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroenterol Hepatol. 2010 May;8(5):471-3. doi: 10.1016/j.cgh.2010.01.007. Epub 2010 Feb 1.

  PMID: 20117243 BACKGROUND

• Dupont HL. Diagnosis and management of Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013 Oct;11(10):1216-23; quiz e73. doi: 10.1016/j.cgh.2013.03.016. Epub 2013 Mar 28.

  PMID: 23542332 BACKGROUND

• 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

• Jiang ZD, Jenq RR, Ajami NJ, Petrosino JF, Alexander AA, Ke S, Iqbal T, DuPont AW, Muldrew K, Shi Y, Peterson C, Do KA, DuPont HL. Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial. PLoS One. 2018 Nov 2;13(11):e0205064. doi: 10.1371/journal.pone.0205064. eCollection 2018.

  PMID: 30388112 DERIVED

Limitations and Caveats

The study would have been improved by increasing the sample size to allow us to randomize subjects to three groups. In addition, while we assume that both procedures preserved spore-forming Clostridia, no spore counts were performed in this 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

  University of Texas School of Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: frozen intestinal bacteria from a healthy donor given by retention enema or lyophilized intestinal bacteria given orally in capsules for therapy in subjects with recurrent C. difficile associated diarrhea (RCDAD)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor
• Expanded Access: Yes

Model Details: Allocation: Randomized Endpoints: Safety, preliminary efficacy in preventing future bouts of CDAD and improvement in intestinal flora diversity Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: May 20, 2015
• Study Start: March 17, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2018
• Last Updated: March 25, 2019
• Results First Posted: March 25, 2019

Record last verified: 2019-03

Locations

US (1)