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Safety and Efficacy of FMT in Individuals With One or More Recurrences of Clostridium Difficile Associated Disease (CDAD)

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ClinicalTrials.gov Identifier: NCT03548051
Recruitment Status : Recruiting
First Posted : June 6, 2018
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
Multi-center, randomized, placebo controlled, partially blinded trial comparing the safety and efficacy of fecal microbiota transplantation versus placebo both delivered by rectal enema in subjects 18 years of age or older with recurrent Clostridium difficile Associated Disease (CDAD). 162 male or female subjects will be enrolled in the study. Enrolled subjects will be randomized at each site to receive either FMT by enema or placebo by enema in a 2:1 ratio. Study duration is 4 years, subject participation duration is approximately 3 years. Primary study objectives: 1) to evaluate the safety of FMT(s) delivered by enema vs. placebo delivered by enema, 2) to determine efficacy of FMT delivered by enema vs. placebo delivered by enema

Condition or disease Intervention/treatment Phase
Clostridial Infection Dysbiosis Probiotic Therapy Procedure: Fecal Microbiota Transplantation (FMT) Drug: Saline Phase 1 Phase 2

Detailed Description:
This is a multi-center, randomized, placebo controlled, partially blinded trial comparing the safety and efficacy of fecal microbiota transplantation versus placebo both delivered by rectal enema in subjects 18 years of age or older with recurrent Clostridium difficile Associated Disease (CDAD). 162 (108 in the FMT group, 54 in the placebo group) male or female subjects will be enrolled in the study. Subjects must have had treatment for most recent CDAD with at least 10 days of either metronidazole po/IV (500 mg tid), oral vancomycin (at least 125 mg qid), or oral fidaxomicin (200 mg bid) and have no diarrheal symptoms (<3 unformed stools per 24 hour period) off antibiotics during the washout period. Enrolled subjects will be randomized at each site to receive either FMT by enema or placebo by enema in a 2:1 ratio. The study is described as partially blinded because by design subjects are to be blinded only to a certain point. Subjects will be followed for clinical response (efficacy) and safety. The study duration is 4 years, subject participation duration is approximately 3 years. Primary study objectives: 1) to evaluate the safety of FMT(s) delivered by enema vs. placebo delivered by enema, 2) to determine efficacy of FMT delivered by enema vs. placebo delivered by enema. Secondary objectives: 1) to evaluate the sustained clinical response rate of FMTs delivered by enema vs. placebo delivered by enema, 2) to evaluate the rate of recurrent CDAD, 3) to evaluate the time to recurrent CDAD.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 1/2 Placebo Controlled, Partially-Blinded Clinical Trial to Assess the Safety and Efficacy of Microbial Restoration by Enema With Banked and Thawed Processed Stool in Individuals With One or More Recurrences of Clostridium Difficile Associated Disease (CDAD)
Actual Study Start Date : September 6, 2018
Estimated Primary Completion Date : September 6, 2021
Estimated Study Completion Date : September 6, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

Arm Intervention/treatment
Experimental: FMT group
100 grams of thawed processed stool diluted into 250 ml of saline and delivered by retention enema given 1-3 hours after loperamide 4 mg po x 1, n=108
Procedure: Fecal Microbiota Transplantation (FMT)
100 grams of thawed processed stool diluted into 250 ml of saline and delivered by retention enema

Experimental: Placebo group
250 ml of saline delivered by retention enema given 1-3 hours after loperamide 4 mg po x 1; if no improvement followed by FMT (100 grams of thawed processed stool diluted into 250 ml of saline and delivered by retention enema given 1-3 hours after loperamide 4 mg po x 1) x 2, n=54
Procedure: Fecal Microbiota Transplantation (FMT)
100 grams of thawed processed stool diluted into 250 ml of saline and delivered by retention enema

Drug: Saline
250 ml of saline delivered by retention enema




Primary Outcome Measures :
  1. Number of subjects with a new onset of related chronic medical condition after completing treatment for recurrent Clostridium Difficile-Associated Diarrhea (CDAD) [ Time Frame: Up to 365 days ]
  2. Number of subjects with a Serious Adverse Events (SAE) (assessed by Adverse Event Grading Scale) after completing treatment for recurrent Clostridium Difficile-Associated Diarrhea (CDAD) [ Time Frame: Up to 365 days ]
  3. Number of subjects with an Adverse Event (AE) (assessed by Adverse Event Grading Scale) after completing treatment for recurrent Clostridium Difficile-Associated Diarrhea (CDAD) [ Time Frame: Up to 30 days ]
  4. Number of subjects with newly acquired transmissible infectious diseases which are considered Adverse Event of Special Interest (AESI), after completing treatment for recurrent Clostridium Difficile-Associated Diarrhea (CDAD) [ Time Frame: Up to 365 days ]
  5. Proportion of subjects with clinical response (no recurrence of Clostridium Difficile-Associated Diarrhea (CDAD)) after randomization [ Time Frame: Up to 30 days ]

Secondary Outcome Measures :
  1. Number of days from randomization until the study day when first Clostridium Difficile-Associated Diarrhea (CDAD) reoccurred after randomization [ Time Frame: Up to 60 days ]
  2. Number of recurrences of Clostridium Difficile-Associated Diarrhea (CDAD) after completing treatment for recurrent CDAD [ Time Frame: Up to 60 days ]
  3. Number of subjects with new onset of related chronic medical condition after completing treatment for recurrent Clostridium Difficile-Associated Diarrhea (CDAD) [ Time Frame: Up to 1095 days ]
  4. Number of subjects with Serious Adverse Events (SAE) assessed by Adverse Event Grading Scale after completing treatment for recurrent Clostridium Difficile-Associated Diarrhea (CDAD) [ Time Frame: Up to 1095 days ]
  5. Proportion of subjects with sustained clinical response (response by day 30 with no recurrence of Clostridium Difficile-Associated Diarrhea (CDAD) through day 60) after randomization [ Time Frame: Up to 60 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Providing permission to access the medical record.
  2. Male or non-pregnant female 18 years or older at the time of enrollment.
  3. Able to provide signed and dated informed consent.
  4. = / > 2 episodes of Clostridium difficile Associated Disease (CDAD) in the past 6 months, including the last episode if present at screening*.

    *Defined by = / > 1 confirmed positive CDAD by diagnostic methods and another occurrence substantiated by medical history.

  5. Completed treatment course of at least 10 days of oral vancomycin, oral/IV metronidazole, or oral fidaxomicin for the most recent episode prior to enrollment.
  6. Controlled diarrheal symptoms (<3 unformed stools per 24 consecutive hour period).
  7. Deemed likely to survive for 1 year after enrollment.
  8. Women of childbearing potential* in sexual relationships with men must use an acceptable method of contraception** from 30 days prior to enrollment until 4 weeks after completing study treatment.

    *Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or < 1 year of the last menses if menopausal. Also includes females who are postmenopausal < 1 year.

    **Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy.

  9. Males must agree to avoid impregnation of women between Day 1 and 28 days following each administration of the study product.
  10. Negative urine or serum pregnancy test within 24 hours of enrollment and randomization.
  11. Is able to provide blood and fecal specimens.
  12. Is able to complete a test of comprehension.

Exclusion Criteria:

  1. Previous FMT within the previous 12 months prior to study enrollment.
  2. Use of the following drugs in last 3 months: such as monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids*, antimetabolites**, calcineurin inhibitors***, mycophenolate mofetil.

    *For example, > 20 mg of prednisone (or equivalent) given daily or on alternative days for 2 weeks or more.

    **, azathioprine, 6-mercaptopurine.

    ***,tacrolimus, cyclosporine.

  3. Requiring antibiotics in the past 2 weeks prior to receiving the enema for a condition other than CDAD or scheduled to be used in the upcoming 2 weeks.
  4. Unable to tolerate enema for any reason.
  5. Any GI cancer in the past year or any actively treated malignancy.
  6. Patients with a history of severe anaphylactic food allergy.
  7. Any history of cirrhosis.
  8. Untreated HIV disease*. *If no HIV screening results are available in the medical record from within the last six months, a HIV screening test will be performed during screening.
  9. Other severe immunosuppression or immunodeficiency.
  10. Severe OR acute disease at the time of enrollment*.

    *Temperature >100.4 degrees Fahrenheit (38.0 degrees Celsius) or heart rate less than 45 bpm or greater than 130 bpm, or systolic blood pressure less than 80 mm Hg or greater than 155 mm Hg, or diastolic blood pressure greater than 100 mm Hg, or at the discretion of the investigator.

  11. Major surgery of the GI tract in the past 6 months.
  12. Having a non tolerance* to or any component of vancomycin, loperamide or GoLYTELY.

    *tolerance is defined as the absence of immunoglobulin E-mediated allergy (e.g., urticaria, angioedema, bronchospasm, or anaphylaxis) and the absence of severe allergy (e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis).

  13. Any history of inflammatory bowel disease (IBD) including ulcerative colitis, Crohn's disease, indeterminate colitis or celiac disease.
  14. Irritable bowel syndrome (IBS) within the past 12 months or any active uncontrolled gastrointestinal disorders or diseases*.

    *GI obstruction, ileus, gastric retention, bowel perforation, toxic colitis or toxic megacolon, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, or refractory/severe Clostridium difficile infection (severe CDAD identified as leukocytosis with a white blood cell count greater than 15,000 cells/mL or an increase in the serum creatinine level to 1.5 times the premorbid level), chronic diarrhea of unknown cause for 6 weeks or more.

  15. Unable to comply with protocol requirements.
  16. Participation in any other clinical drug research trial within 30 days prior to enrollment or for 1 year after enrollment that might interfere with the safety and efficacy assessment.
  17. A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03548051


Contacts
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Contact: Nadine Rouphael 14047121435 nroupha@emory.edu

Locations
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United States, Georgia
Emory Vaccine Center - The Hope Clinic Recruiting
Decatur, Georgia, United States, 30030-1705
United States, North Carolina
Duke Human Vaccine Institute - Duke Vaccine and Trials Unit Recruiting
Durham, North Carolina, United States, 27708
United States, Tennessee
Vanderbilt University Medical Center - Infectious Diseases Recruiting
Nashville, Tennessee, United States, 37232-0011
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03548051     History of Changes
Other Study ID Numbers: 13-0045
HHSN272201300017I
First Posted: June 6, 2018    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Clinical Trial
Clostridium difficile
Clostridium difficle Associated Disease (CDAD)
Efficacy
Fecal Microbiota Transplantation (FMT)
Microbial Restoration
Partially-Blinded
Placebo
Safety
Stool
Additional relevant MeSH terms:
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Clostridium Infections
Recurrence
Dysbiosis
Disease Attributes
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections