Fecal Microbiota Transplant for Primary CDI
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/3/2019 |
| Start Date: | April 2019 |
| End Date: | April 2020 |
| Contact: | Tamar Barlam, MD MSC |
| Email: | tamar.barlam@bmc.org |
| Phone: | 617 414 5190 |
Fecal Microbiota Transplant (FMT) After Treatment for a First Episode of Clostridium Difficile Infection (CDI)
Clostridium difficile infection (CDI) is one of the most urgent health threats in the U.S.
associated with antibiotic use. After an initial episode, disease recurrence is high and
relapses can occur in 20-30% of people treated with oral vancomycin. An antibiotic course can
affect the gut microbiome for years, and patients with CDI have additional dysbiosis of their
gut flora. Oral vancomycin perturbs the gut microbiome further. Restoration of the microbiome
with Fecal Microbiota Transplant (FMT) has been proven a highly efficacious and
cost-effective treatment for recurrent CDI. FMT has had very limited study for a primary
episode of CDI to date because an endoscopic procedure was the recommended route of delivery.
However, FMT is now available via frozen oral capsules and has been shown to be non-inferior
to FMT via colonoscopy in randomized controlled trials.
The investigators hypothesize that outcomes after a first episode of CDI can be improved if
the microbiome is restored with oral FMT. It is further hypothesized that this will
compensate for any additional microbiome perturbation caused by administration of oral
vancomycin and decrease the likelihood of recurrence. Because the hypothesis is based on
restoration of the microbiome, the investigators propose this proof-of-concept pilot study to
examine whether FMT administered after oral vancomycin therapy for primary CDI restores
microbiome diversity compared to patients who do not receive FMT. Because of the potential
health benefits, this approach deserves further study. The results from this pilot study on
the microbiome diversity as well as the surveys to be conducted about GI symptomatology
(e.g., diarrhea, abdominal pain, bloating), CDI recurrence and healthcare utilization, would
provide preliminary data to support a randomized controlled, multicenter clinical trial.
associated with antibiotic use. After an initial episode, disease recurrence is high and
relapses can occur in 20-30% of people treated with oral vancomycin. An antibiotic course can
affect the gut microbiome for years, and patients with CDI have additional dysbiosis of their
gut flora. Oral vancomycin perturbs the gut microbiome further. Restoration of the microbiome
with Fecal Microbiota Transplant (FMT) has been proven a highly efficacious and
cost-effective treatment for recurrent CDI. FMT has had very limited study for a primary
episode of CDI to date because an endoscopic procedure was the recommended route of delivery.
However, FMT is now available via frozen oral capsules and has been shown to be non-inferior
to FMT via colonoscopy in randomized controlled trials.
The investigators hypothesize that outcomes after a first episode of CDI can be improved if
the microbiome is restored with oral FMT. It is further hypothesized that this will
compensate for any additional microbiome perturbation caused by administration of oral
vancomycin and decrease the likelihood of recurrence. Because the hypothesis is based on
restoration of the microbiome, the investigators propose this proof-of-concept pilot study to
examine whether FMT administered after oral vancomycin therapy for primary CDI restores
microbiome diversity compared to patients who do not receive FMT. Because of the potential
health benefits, this approach deserves further study. The results from this pilot study on
the microbiome diversity as well as the surveys to be conducted about GI symptomatology
(e.g., diarrhea, abdominal pain, bloating), CDI recurrence and healthcare utilization, would
provide preliminary data to support a randomized controlled, multicenter clinical trial.
Population: Patients >= 18 years hospitalized at Boston Medical Center (BMC) with a first
documented episode of CDI.
Intervention: 30 FMT capsules administered orally under direct observation within 7 days of
completion of 10-14 day treatment of oral vancomycin for CDI.
Objectives:
1. To characterize the microbial diversity in stool samples from subjects with a primary
episode of CDI before and after oral vancomycin and determine the impact of FMT after
completion of oral vancomycin course.
2. To characterize the feasibility and tolerability of FMT after completion of a course of
oral vancomycin therapy for primary CDI, and to describe 30-day hospital readmission and
gastrointestinal symptomatology and/or CDI recurrence during 60-day follow-up.
Design/Methodology:
15 subjects will be enrolled who are hospitalized at BMC for a primary episode of CDI. A
discard aliquot from baseline stool samples obtained clinically for diagnosis will be frozen.
Subjects will receive the standard of care treatment (oral vancomycin for 10-14 days) and
within 7 days following completion will receive oral FMT during a 2 hour visit in the
Infectious Disease (ID) Clinical Trials Unit. An additional 5 subjects will be enrolled as
controls. Stool samples will be collected at time of CDI diagnosis and again 3 weeks after
FMT for intervention group and 4 weeks after completion of oral vancomycin treatment for
control subjects. The post-treatment samples will be obtained by the patient using special
stool sample collection kits known as RNAlater kits (ribonucleic acid stabilization). These
contain a liquid nontoxic tissue storage reagent known as RNAlater and helps preserve the
stool sample. The subjects will mail this stool sample to the BMC Clinical Trials Unit (CTU)
where it will aliquoted, centrifuged and frozen.
Samples will be processed at a collaborating lab at Tufts to characterize the fecal
microbiome pre- and post oral FMT.
Study personnel will contact participants via telephone 60 days after FMT dosing to
administer a follow-up survey (including questions on residual symptoms. CDI recurrence,
re-hospitalization, adverse events and FMT acceptability).
Total Study Duration: Anticipated time: 12 months
Subject Participation Duration: The researchers anticipate a period of 1-2 hours while an
inpatient for the screening and consent process, 2 hours for the CTU visit for FMT and 20-30
minutes responding to a follow up telephone survey. Total time in the study from enrollment
to completion of follow-up will be approximately 3 months and will include 10-14 days of CDI
treatment with oral vancomycin (per standard of care treatment), the FMT administration and a
60 day follow up.
documented episode of CDI.
Intervention: 30 FMT capsules administered orally under direct observation within 7 days of
completion of 10-14 day treatment of oral vancomycin for CDI.
Objectives:
1. To characterize the microbial diversity in stool samples from subjects with a primary
episode of CDI before and after oral vancomycin and determine the impact of FMT after
completion of oral vancomycin course.
2. To characterize the feasibility and tolerability of FMT after completion of a course of
oral vancomycin therapy for primary CDI, and to describe 30-day hospital readmission and
gastrointestinal symptomatology and/or CDI recurrence during 60-day follow-up.
Design/Methodology:
15 subjects will be enrolled who are hospitalized at BMC for a primary episode of CDI. A
discard aliquot from baseline stool samples obtained clinically for diagnosis will be frozen.
Subjects will receive the standard of care treatment (oral vancomycin for 10-14 days) and
within 7 days following completion will receive oral FMT during a 2 hour visit in the
Infectious Disease (ID) Clinical Trials Unit. An additional 5 subjects will be enrolled as
controls. Stool samples will be collected at time of CDI diagnosis and again 3 weeks after
FMT for intervention group and 4 weeks after completion of oral vancomycin treatment for
control subjects. The post-treatment samples will be obtained by the patient using special
stool sample collection kits known as RNAlater kits (ribonucleic acid stabilization). These
contain a liquid nontoxic tissue storage reagent known as RNAlater and helps preserve the
stool sample. The subjects will mail this stool sample to the BMC Clinical Trials Unit (CTU)
where it will aliquoted, centrifuged and frozen.
Samples will be processed at a collaborating lab at Tufts to characterize the fecal
microbiome pre- and post oral FMT.
Study personnel will contact participants via telephone 60 days after FMT dosing to
administer a follow-up survey (including questions on residual symptoms. CDI recurrence,
re-hospitalization, adverse events and FMT acceptability).
Total Study Duration: Anticipated time: 12 months
Subject Participation Duration: The researchers anticipate a period of 1-2 hours while an
inpatient for the screening and consent process, 2 hours for the CTU visit for FMT and 20-30
minutes responding to a follow up telephone survey. Total time in the study from enrollment
to completion of follow-up will be approximately 3 months and will include 10-14 days of CDI
treatment with oral vancomycin (per standard of care treatment), the FMT administration and a
60 day follow up.
Inclusion Criteria:
- Diagnosis of primary clostridium difficile infection (CDI) defined by the presence of
diarrhea and a positive C. difficile Polymerase chain reaction (PCR) test
- Admitted to Boston Medical Center
- English speaking
Exclusion Criteria:
- Primary CDI treatment failure
- History of CDI
- Diagnosis of inflammatory bowel disease, immunocompromised state, or active malignancy
- Dysphagia: oropharyngeal, esophageal, functional, neuromuscular (e.g. stroke, multiple
sclerosis, ALS), or patient shows evidence of dysphagia when the 'safety test' capsule
is administered
- History of aspiration
- History of gastroparesis
- History of intestinal obstruction
- Severe food allergy (e.g. anaphylaxis or anaphylactoid reaction) Adverse event
attributable to a previous FMT
- Patients with allergies to sodium chloride, glycerol, theobroma oil, hide bovine
gelatin, sodium lauryl sulfate, Food, Drugs & Cosmetics certified colorants (FD&C), or
titanium dioxide, all ingredients Generally Recognized As Safe (GRAS)
- History of ongoing antibiotic use (e.g. nitrofurantoin for urinary tract infection
[UTI] prophylaxis) Currently pregnant or breastfeeding -Any condition for which the
treating physician thinks the treatment may pose a health risk (e.g. severely
immunocompromised)-
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