Clostridium Difficile InfectionPhase 1NCT03827447
Vancomycin for the Treatment of NAAT(+)/Toxin(-) C. Difficile
A Phase 1 study testing Vancomycin Oral Capsule in people with Clostridium Difficile Infection, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This study proposes to: 1. Characterize the impact of oral vancomycin on C. difficile loads after end of treatment compared to a placebo group. 2. Determine the effect of oral vancomycin on structural and functional microbiome changes after end of treatment compared to a placebo group. 3. 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?
- Vancomycin Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2019to 30 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Must be at least 18 years of age at time of consent.
- Presence of loose stools triggering clinical C. difficile NAAT/toxin EIA testing.
- Having both C. difficile NAAT (+) and C. difficile toxin EIA (-).
- Admitted outside the hematology-oncology unit.
- Must be willing to keep a study supplied drug diary
Who cannot join
- Presence of sepsis. Sepsis will be defined as a Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more as per 2016 definitions.
- Inability to take oral medications.
- Unwillingness or inability to provide written informed consent.
- Has a documented allergy to vancomycin.
- Has a documented life expectancy shorter than treatment course (14 days).
- Unwilling or unable to collect stool samples in the outpatient setting after discharge.
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- Diagnosis of C. difficile colitis [NAAT(+) and toxin EIA(+)] in the preceding 3 months from enrollment.
- Received oral vancomycin during their current hospitalization, excluding empiric treatment given while pending C. difficile NAAT/toxin EIA results. Intravenous vancomycin is not an exclusion criterion.
- Women known to be pregnant or lactating during the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, 53226
About this study
Official title: Randomized Double Blind Placebo Controlled Trial for the Treatment of NAAT(+)/Toxin EIA(-) Clostridium Difficile
This study proposes to:
- Characterize the impact of oral vancomycin on C. difficile loads after end of treatment compared to a placebo group.
- Determine the effect of oral vancomycin on structural and functional microbiome changes after end of treatment compared to a placebo group.
- Characterize the impact of oral vancomycin against a placebo group on the daily frequency of loose stools by the end of treatment.
Read the detailed description
Clostridium difficile infection (CDI) is considered the most frequent healthcare associated infection in the US, causing almost half a million cases per year with an estimated annual cost of 4.8 billion dollars. Despite the existence of a few treatment options against CDI, yearly attributable deaths are estimated at 29,300 in the US. From April 2014 to April 2016, Froedtert Health reported 899 CDIs. Over half of these events are NAAT (Nucleic Acid Amplification Test)(+)/EIA (Enzyme immunoassay)(-) events. To test for CDI, NAAT followed by EIA is used in a Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) and are among the most accurate methods for Clostridium difficile infection (CDI) diagnosis. There is currently uncertainty on how to treat these CDI events.
The primary outcome of this randomized double blind controlled intervention trial will be changes in C. difficile (Clostridium difficile) loads between day 1 and day 14 and changes in C. difficile load between day 14 and day 28. Thirty patients with documented C. difficile will be randomized to either 14 days of vancomycin or placebo capsules. Block randomization will be used to assign patients to the treatment or placebo arms. Randomized assignments will be placed in sealed envelopes which will only be handled by the research pharmacist. Study related stool collections will be obtained on days 1, 7, 14, 21, and 28 (+/- 2days) [Day 1=first day study drug was administered]. Patients will be followed for 90 days starting on day 1. Patients unable to complete at least 7 days of study treatment will be removed from analysis and replaced.
- Conditions
- Clostridium Difficile Infection
- Being tested
- Vancomycin Oral Capsule, Placebo Oral Capsule
- Keywords
- Clostridium Difficile, Metabolomics, Vancomycin, Microbiome
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vancomycin Oral CapsuleDrug
Also called Vancocin
125 mg capsules every 6 hours for 14 days.
Placebo Oral CapsuleDrug
Gelatin pill manufactured to mimic 125 mg Vancomycin oral capsule
| Study group | Role | What they receive |
|---|---|---|
| Drug: Vancomycin Group | Active comparator | Subjects will receive oral vancomycin capsules by mouth, 125 mg every 6 hours for 14 days. Receives: Drug: Vancomycin Oral Capsule |
| Drug: Placebo Group | Placebo comparator | Subjects will receive a placebo oral capsule by mouth every 6 hours for 14 days. The placebo oral capsule is manufactured by Study Site's pharmacy to be identical in size, shape, color, appearance and taste as the drug comparator Receives: Drug: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the change in C. difficile loads between the vancomycin vs. placebo group.
Compare the impact of vancomycin vs placebo on changes in C. difficile load from stool samples collected on Day 1 to end-of-treatment (Day 14) and to Day 28 using quantitative Polymerase Chain Reaction (qPCR).
Measured: Day 1- Day 28
Determine the long-term persistence of C. difficile from the change in qPCR levels between the vancomycin vs. placebo group
Establish the long-term persistence of C. difficile by qPCR from stool samples collected at Day 1, 7, 14, 21, 28, and 90 between the vancomycin and placebo group.
Measured: Day 1 - Day 90
Secondary outcomes (6)
Characterize the change on structural alterations of the microbiome after end of treatment between the vancomycin vs. placebo groups through 16S rRNA sequencing.
Structural alterations of the microbiome after end of treatment will be determined using 16S rRNA sequencing from stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90. Structural alterations will be defined according to the Shannon Diversity Index.
Measured: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in bile acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring bile acids. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
Measured: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in amino acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring amino acids. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
Measured: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in sugars in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring sugars. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
Measured: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in lipids from Day 1 to Day 90 in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring lipids. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
Measured: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in frequency of bowel movements in the oral vancomycin vs. placebo groups.
Characterize the impact of oral vancomycin against a placebo group on the daily frequency of bowel movements by the end of treatment. This scale goes from 0 to >20 in increments of 1. Data will be analyzed over time as a slope for each patient. The closer to 1 per 24 hours the better the outcome. Data will be obtained from patient self-reports using study questionnaires on Days 1, 7, 14, 21, 28 \& 90.
Measured: Day 1 - Day 90 past the beginning of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start17 Jul 2019
- Primary completion1 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be divided into 2 groups, one receiving oral vancomycin and the other placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silvia Munoz-Price, Medical College of Wisconsin
- Investigators
- Silvia Munoz-Price, M.D., Ph.D., Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03827447
- Sponsor's protocol ID
- PRO00033844
- Status last verified
- Oct 2021
- First submitted
- 21 Jan 2019
- Last updated
- 20 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Participant data to be shared would consist of age categories, genders, treatment groups, Clostridium difficile status, microbiome profile and metabolic profile. The data will be anonymized to prevent the identification of individual patients from the data provided. The data would be made available through contacting the principal investigator directly.
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Double Blind Placebo Controlled Trial for the Treatment of NAAT(+)/Toxin EIA(-) Clostridium Difficile
- ClinicalTrials.gov ID
- NCT03827447
- Acronym / sponsor ID
- PRO00033844
- Conditions
- Clostridium Difficile Infection
- Keywords
- Clostridium Difficile, Metabolomics, Vancomycin, Microbiome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 1 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study proposes to:
- Characterize the impact of oral vancomycin on C. difficile loads after end of treatment compared to a placebo group.
- Determine the effect of oral vancomycin on structural and functional microbiome changes after end of treatment compared to a placebo group.
- Characterize the impact of oral vancomycin against a placebo group on the daily frequency of loose stools by the end of treatment.
Detailed description
Clostridium difficile infection (CDI) is considered the most frequent healthcare associated infection in the US, causing almost half a million cases per year with an estimated annual cost of 4.8 billion dollars. Despite the existence of a few treatment options against CDI, yearly attributable deaths are estimated at 29,300 in the US. From April 2014 to April 2016, Froedtert Health reported 899 CDIs. Over half of these events are NAAT (Nucleic Acid Amplification Test)(+)/EIA (Enzyme immunoassay)(-) events. To test for CDI, NAAT followed by EIA is used in a Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) and are among the most accurate methods for Clostridium difficile infection (CDI) diagnosis. There is currently uncertainty on how to treat these CDI events.
The primary outcome of this randomized double blind controlled intervention trial will be changes in C. difficile (Clostridium difficile) loads between day 1 and day 14 and changes in C. difficile load between day 14 and day 28. Thirty patients with documented C. difficile will be randomized to either 14 days of vancomycin or placebo capsules. Block randomization will be used to assign patients to the treatment or placebo arms. Randomized assignments will be placed in sealed envelopes which will only be handled by the research pharmacist. Study related stool collections will be obtained on days 1, 7, 14, 21, and 28 (+/- 2days) [Day 1=first day study drug was administered]. Patients will be followed for 90 days starting on day 1. Patients unable to complete at least 7 days of study treatment will be removed from analysis and replaced.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Patients will be divided into 2 groups, one receiving oral vancomycin and the other placebo.
| Arm | Type | Receives |
|---|---|---|
| Drug: Vancomycin Group | Active comparator | Drug: Vancomycin Oral CapsuleSubjects will receive oral vancomycin capsules by mouth, 125 mg every 6 hours for 14 days. |
| Drug: Placebo Group | Placebo comparator | Drug: Placebo Oral CapsuleSubjects will receive a placebo oral capsule by mouth every 6 hours for 14 days. The placebo oral capsule is manufactured by Study Site's pharmacy to be identical in size, shape, color, appearance and taste as the drug comparator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Must be at least 18 years of age at time of consent.
- Presence of loose stools triggering clinical C. difficile NAAT/toxin EIA testing.
- Having both C. difficile NAAT (+) and C. difficile toxin EIA (-).
- Admitted outside the hematology-oncology unit.
- Must be willing to keep a study supplied drug diary
Key exclusion criteria (9 listed)
- Presence of sepsis. Sepsis will be defined as a Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more as per 2016 definitions.
- Inability to take oral medications.
- Unwillingness or inability to provide written informed consent.
- Has a documented allergy to vancomycin.
- Has a documented life expectancy shorter than treatment course (14 days).
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 |
|---|---|---|
| Vancomycin Oral CapsuleAlso: Vancocin125 mg capsules every 6 hours for 14 days. | Drug | Drug: Vancomycin Group |
| Placebo Oral CapsuleGelatin pill manufactured to mimic 125 mg Vancomycin oral capsule | Drug | Drug: Placebo Group |
Primary outcome
Determine the change in C. difficile loads between the vancomycin vs. placebo group.
Time frame: Day 1- Day 28
Compare the impact of vancomycin vs placebo on changes in C. difficile load from stool samples collected on Day 1 to end-of-treatment (Day 14) and to Day 28 using quantitative Polymerase Chain Reaction (qPCR).
Determine the long-term persistence of C. difficile from the change in qPCR levels between the vancomycin vs. placebo group
Time frame: Day 1 - Day 90
Establish the long-term persistence of C. difficile by qPCR from stool samples collected at Day 1, 7, 14, 21, 28, and 90 between the vancomycin and placebo group.
6 secondary outcomes
Characterize the change on structural alterations of the microbiome after end of treatment between the vancomycin vs. placebo groups through 16S rRNA sequencing.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in bile acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in amino acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in sugars in the oral vancomycin vs. placebo groups by mass spectrometry.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in lipids from Day 1 to Day 90 in the oral vancomycin vs. placebo groups by mass spectrometry.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in frequency of bowel movements in the oral vancomycin vs. placebo groups.
Time frame: Day 1 - Day 90 past the beginning of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2021.
- Individual participant dataSharing planned: No. Participant data to be shared would consist of age categories, genders, treatment groups, Clostridium difficile status, microbiome profile and metabolic profile. The data will be anonymized to prevent the identification of individual patients from the data provided. The data would be made available through contacting the principal investigator directly.
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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.
Silvia Munoz-Price, M.D., Ph.D. principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vancomycin Oral Capsule in people with Clostridium Difficile Infection, run by Medical College of Wisconsin 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 5 inclusion and 9 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: finished, as of the sponsor's last update on 20 Oct 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determine the change in C. difficile loads between the vancomycin vs. placebo group. (time frame: Day 1- Day 28). The study lists 2 primary outcomes in all. 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 20 Oct 2021.