Clostridium Difficile InfectionPhase 1/2NCT03795233
Fecal Microbiota Transplant for Primary CDI
A Phase 1/2 study testing Fecal microbiota transplant G3 capsules and Oral Vancomycin alone in people with Clostridium Difficile Infection, run by Boston Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Infection
- What is being tested?
- Fecal microbiota transplant G3 capsules and Oral Vancomycin alone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Aug 2019to 15 Jan 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)-
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
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:
- 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.
- 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.
- Conditions
- Clostridium Difficile Infection
- Being tested
- Fecal microbiota transplant G3 capsules, Oral Vancomycin alone
- Keywords
- Fecal Microbiota Transplant (FMT), Vancomycin, Dysbiosis, fecal microbiome, C difficile infection
- Medical subject headings
- Clostridium Infections, Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal microbiota transplant G3 capsulesBiological
Also called FMT
After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation
Oral Vancomycin aloneOther
Also called Oral Vancocin alone
Standard of care will be provided with oral vancomycin therapy.
| Study group | Role | What they receive |
|---|---|---|
| Fecal microbiota transplantation | Experimental | Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection. Receives: Biological: Fecal microbiota transplant G3 capsules |
| Oral vancomycin alone (Control) | Active comparator | Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection. Receives: Other: Oral Vancomycin alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stool Microbiome With and Without FMT Administration
The stool microbiome in participants who receive additional FMT at end of Clostridium difficile infection (CDI) treatment with oral vancomycin will be compared to the stool microbiome in participants with standard treatment or oral vancomycin alone
Measured: 11 months
Secondary outcomes (5)
Feasibility of Administering FMT After Completion of a Course of Oral Vancomycin Therapy
The number and proportion of FMT pills participants ingest after completion of a course of oral vancomycin therapy will be documented.
Measured: 12 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of FMT After a Course of Oral Vancomycin Therapy
Study participants will be monitored for any adverse events to FMT such as nausea or vomiting, abdominal pain or diarrhea.
Measured: During test dose, during 90 minutes of FMT administration, 30 minutes after FMT administration, 48-72 hours after FMT administration
Incidence of Gastrointestinal Symptomatology Based on a Survey After CDI
A detailed survey with 15 questions will be administered on GI symptoms Physicians will go over any significant adverse events to determine if they are related, possibly related or unrelated to oral FMT administration
Measured: 60 days
CDI Recurrence
Patients will be monitored for recurrent C difficile infection defined as non-resolution or recurrence of GI symptoms (abdominal pain, diarrhea etc) and/or a positive stool C difficile test The proportion of participants with CDI recurrence will be documented.
Measured: 60 days
Number of Hospital Readmissions After Treatment
The number of hospital readmissions within 30 days after CDI treatment per patient history and chart review will be obtained
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2019
- Study start23 Aug 2019
- Primary completion15 Jan 2021
- Study completion15 Jan 2021
Why it stopped: The study was terminated after a covid-related suspension and the unavailability of drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tamar Barlam, MD MSC, Principal investigator, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03795233
- Sponsor's protocol ID
- H-37574
- Status last verified
- Nov 2021
- First submitted
- 21 Nov 2018
- Last updated
- 15 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fecal Microbiota Transplant (FMT) After Treatment for a First Episode of Clostridium Difficile Infection (CDI)
- ClinicalTrials.gov ID
- NCT03795233
- Acronym / sponsor ID
- H-37574
- Conditions
- Clostridium Difficile Infection
- Keywords
- Fecal Microbiota Transplant (FMT), Vancomycin, Dysbiosis, fecal microbiome, C difficile infection
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated after a covid-related suspension and the unavailability of drug.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Boston Medical CenterUniversity, hospital or other
- Study start
- 23 Aug 2019 (actual)
- Primary completion
- 15 Jan 2021 (actual)
- Study completion
- 15 Jan 2021 (actual)
- First posted
- 7 Jan 2019 (actual)
- Results
- Posted 15 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal microbiota transplantation | Experimental | Biological: Fecal microbiota transplant G3 capsulesFecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection. |
| Oral vancomycin alone (Control) | Active comparator | Other: Oral Vancomycin aloneOral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal microbiota transplant G3 capsulesAlso: FMTAfter standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation | Biological | Fecal microbiota transplantation |
| Oral Vancomycin aloneAlso: Oral Vancocin aloneStandard of care will be provided with oral vancomycin therapy. | Other | Oral vancomycin alone (Control) |
Primary outcome
Stool Microbiome With and Without FMT Administration
Time frame: 11 months
The stool microbiome in participants who receive additional FMT at end of Clostridium difficile infection (CDI) treatment with oral vancomycin will be compared to the stool microbiome in participants with standard treatment or oral vancomycin alone
5 secondary outcomes
Feasibility of Administering FMT After Completion of a Course of Oral Vancomycin Therapy
Time frame: 12 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of FMT After a Course of Oral Vancomycin Therapy
Time frame: During test dose, during 90 minutes of FMT administration, 30 minutes after FMT administration, 48-72 hours after FMT administration
Incidence of Gastrointestinal Symptomatology Based on a Survey After CDI
Time frame: 60 days
CDI Recurrence
Time frame: 60 days
Number of Hospital Readmissions After Treatment
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tamar Barlam, MD MSC principal investigator
Boston Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fecal microbiota transplant G3 capsules and Oral Vancomycin alone in people with Clostridium Difficile Infection, run by Boston Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stool Microbiome With and Without FMT Administration (time frame: 11 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2021.