Clostridium DifficilePhase 4NCT01901276
Effects of Gastric Acid on Colonic Microbiome
A Phase 4 study testing Omeprazole 40 mg bid in people with Clostridium Difficile, run by Daniel Freedberg, MD at 1 site in United States.
Trial summary
The colonic microbiome is essential in human health and disease. Clostridium difficile-associated diarrhea (CDAD), a highly morbid form of infectious diarrhea, is caused by antibiotics which perturb the microbiome and allow C. difficile to proliferate. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Clostridium Difficile
- What is being tested?
- Omeprazole 40 mg bid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Mar 2015
- Phase
- Phase 4
- 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
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 or more years old
- Able to give informed consent
Who cannot join
- Use of systemic antibiotics within the past year
- Use of acid suppression medications (PPIs or H2-receptor antagonists) within the past year (antacids permitted if more than one month from date of enrollment)
- History of chronic gastrointestinal mucosal disease (e.g. inflammatory bowel disease, celiac disease, microscopic colitis)
- Any clinically significant or uncontrolled major morbidity, including but not limited to serious cardiac or respiratory disease or uncontrolled HIV
- Abnormal bowel frequency (minimum once every 2 days, maximum 3 times per day)
- Use of clopidogrel or medications with potential significant interaction with PPIs
Show all 11Show fewer
- Osteoperosis or history of non-traumatic bone fracture
- History of adverse reactions to PPIs
- Initiation of any new medication within the month prior to enrollment
- Pregnancy
- Inability to give informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of Gastric Acid Suppression on the Colonic Microbiome
The colonic microbiome is essential in human health and disease. Clostridium difficile-associated diarrhea (CDAD), a highly morbid form of infectious diarrhea, is caused by antibiotics which perturb the microbiome and allow C. difficile to proliferate. Proton pump inhibitors (PPIs) are powerful suppressors of gastric acid and among the most common medicines in the United States. Dozens of observational studies show that longterm PPI use is associated with CDAD. However, the mechanism by which PPIs cause CDAD is unknown. We believe that PPIs cause CDAD by inducing alterations in the human colonic microbiome. We will confirm or refute the hypothesized mechanism for the association between PPIs and CDAD using an unblinded, single-armed study design. We will use pyrosequencing of the hypervariable V4 region of the bacterial 16S ribosomal subunit gene in human fecal samples to describe the colonic flora. We will collect fecal samples from volunteers before and after PPIs given for different durations and test the microbiome to determine 1) whether PPIs diminish overall diversity, 2) whether PPIs diminish relative abundance of Bacteroidetes, 3) whether increased duration of PPIs affects diversity, and 4) whether there is recovery of diversity after completing a defined course of PPIs. We believe that PPIs will cause a pattern of diminished overall microbiome diversity and reduced anaerobes - the same pattern seen after use of antibiotics. Furthermore, we believe that increased PPI duration will further diminish diversity and that the microbiome will return to pre-PPI levels of diversity after PPIs are stopped. These results will facilitate biologically-based clinical interventions to reduce rates of CDAD among patients who require acid suppression.
Read the detailed description
Study Design We will recruit 12 adult volunteers for a crossover study with a total duration of 12 weeks. Subjects will be observed off of PPIs for 4 weeks and then will be placed on PPIs for 4 weeks. Subsequently, subjects will be randomized to receive an additional 4 weeks of PPIs or no therapy. Stool samples will be collected at 4 separate time points.
Study Outcomes and Statistical Analyses The primary outcome will be change in overall diversity of fecal flora after 4 weeks of PPIs compared to 4 weeks of no acid suppression. Additional outcomes to be assessed include the effect of PPIs on the relative abundance of Bacteroidetes at week 4 and change in the diversity of fecal flora at week 8.
- Conditions
- Clostridium Difficile
- Being tested
- Omeprazole 40 mg bid
- Keywords
- Proton Pump Inhibitors, Microbiome, Clostridium difficile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omeprazole 40 mg bidDrug
Also called Brand name: Prilosec
As above.
| Study group | Role | What they receive |
|---|---|---|
| Omeprazole 40 mg bid x 4-8 weeks | Experimental | See study description for further details. Receives: Drug: Omeprazole 40 mg bid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Shannon Diversity Index Measuring Change in Microbiome Diversity
In order to assess the diversity of the colonic microbiome, the Shannon diversity index will be calculated for each subject:
- After four weeks of no acid suppression (Week 0 vs. Week 4)
- After four weeks of twice daily PPI (Week 4 vs. Week 8)
The Shannon diversity index is a mathematical measure of species diversity in a given community. The Shannon index is calculated as: -∑[(pi)×ln(pi)] where H is the Shannon diversity index, and pi is the proportion of individuals of i-th species in a whole community. The minimum value of the Shannon diversity index is 0, which indicates there's no diversity - only one species is found in that habitat. There is no upper limit to the Shannon index. The higher the value of H, the higher the diversity of species in a particular community.
Measured: Baseline (Week 0), Week 4, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2013 (estimated)
- Study startAug 2013
- Primary completionMar 2015
- Study completionMar 2015
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium DifficileStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daniel Freedberg, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Daniel Freedberg, MD, Columbia University
- Investigators
- Julian A Abrams, MD, MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01901276
- Sponsor's protocol ID
- AAAL3307
- Status last verified
- Jul 2024
- First submitted
- 12 Jul 2013
- Last updated
- 15 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Refer to the published study results for summary data.
Publications
Freedberg DE, Toussaint NC, Chen SP, Ratner AJ, Whittier S, Wang TC, Wang HH, Abrams JA. Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial. Gastroenterology. 2015 Oct;149(4):883-5.e9. doi: 10.1053/j.gastro.2015.06.043. Epub 2015 Jul 9.
PubMed 26164495
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Gastric Acid Suppression on the Colonic Microbiome
- ClinicalTrials.gov ID
- NCT01901276
- Acronym / sponsor ID
- AAAL3307
- Conditions
- Clostridium Difficile
- Keywords
- Proton Pump Inhibitors, Microbiome, Clostridium difficile
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Daniel Freedberg, MDUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 17 Jul 2013 (estimated)
- Results
- Posted 15 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The colonic microbiome is essential in human health and disease. Clostridium difficile-associated diarrhea (CDAD), a highly morbid form of infectious diarrhea, is caused by antibiotics which perturb the microbiome and allow C. difficile to proliferate. Proton pump inhibitors (PPIs) are powerful suppressors of gastric acid and among the most common medicines in the United States. Dozens of observational studies show that longterm PPI use is associated with CDAD. However, the mechanism by which PPIs cause CDAD is unknown. We believe that PPIs cause CDAD by inducing alterations in the human colonic microbiome. We will confirm or refute the hypothesized mechanism for the association between PPIs and CDAD using an unblinded, single-armed study design. We will use pyrosequencing of the hypervariable V4 region of the bacterial 16S ribosomal subunit gene in human fecal samples to describe the colonic flora. We will collect fecal samples from volunteers before and after PPIs given for different durations and test the microbiome to determine 1) whether PPIs diminish overall diversity, 2) whether PPIs diminish relative abundance of Bacteroidetes, 3) whether increased duration of PPIs affects diversity, and 4) whether there is recovery of diversity after completing a defined course of PPIs. We believe that PPIs will cause a pattern of diminished overall microbiome diversity and reduced anaerobes - the same pattern seen after use of antibiotics. Furthermore, we believe that increased PPI duration will further diminish diversity and that the microbiome will return to pre-PPI levels of diversity after PPIs are stopped. These results will facilitate biologically-based clinical interventions to reduce rates of CDAD among patients who require acid suppression.
Detailed description
Study Design We will recruit 12 adult volunteers for a crossover study with a total duration of 12 weeks. Subjects will be observed off of PPIs for 4 weeks and then will be placed on PPIs for 4 weeks. Subsequently, subjects will be randomized to receive an additional 4 weeks of PPIs or no therapy. Stool samples will be collected at 4 separate time points.
Study Outcomes and Statistical Analyses The primary outcome will be change in overall diversity of fecal flora after 4 weeks of PPIs compared to 4 weeks of no acid suppression. Additional outcomes to be assessed include the effect of PPIs on the relative abundance of Bacteroidetes at week 4 and change in the diversity of fecal flora at week 8.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Omeprazole 40 mg bid x 4-8 weeks | Experimental | Drug: Omeprazole 40 mg bidSee study description for further details. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 18 or more years old
- Able to give informed consent
Key exclusion criteria (11 listed)
- Use of systemic antibiotics within the past year
- Use of acid suppression medications (PPIs or H2-receptor antagonists) within the past year (antacids permitted if more than one month from date of enrollment)
- History of chronic gastrointestinal mucosal disease (e.g. inflammatory bowel disease, celiac disease, microscopic colitis)
- Any clinically significant or uncontrolled major morbidity, including but not limited to serious cardiac or respiratory disease or uncontrolled HIV
- Abnormal bowel frequency (minimum once every 2 days, maximum 3 times per day)
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 |
|---|---|---|
| Omeprazole 40 mg bidAlso: Brand name: PrilosecAs above. | Drug | Omeprazole 40 mg bid x 4-8 weeks |
Primary outcome
Shannon Diversity Index Measuring Change in Microbiome Diversity
Time frame: Baseline (Week 0), Week 4, Week 8
In order to assess the diversity of the colonic microbiome, the Shannon diversity index will be calculated for each subject: * After four weeks of no acid suppression (Week 0 vs. Week 4) * After four weeks of twice daily PPI (Week 4 vs. Week 8) The Shannon diversity index is a mathematical measure of species diversity in a given community. The Shannon index is calculated as: -∑[(pi)×ln(pi)] where H is the Shannon diversity index, and pi is the proportion of individuals of i-th species in a whole community. The minimum value of the Shannon diversity index is 0, which indicates there's no diversity - only one species is found in that habitat. There is no upper limit to the Shannon index. The higher the value of H, the higher the diversity of species in a particular community.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26164495Freedberg DE, Toussaint NC, Chen SP, Ratner AJ, Whittier S, Wang TC, Wang HH, Abrams JA. Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial. Gastroenterology. 2015 Oct;149(4):883-5.e9. doi: 10.1053/j.gastro.2015.06.043. Epub 2015 Jul 9.
- Individual participant dataSharing planned: No. Refer to the published study results for summary data.
Related trials for Clostridium Difficile
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Epidemiology of Clostridioides Difficile Infection (CDI) in Long-term Care Facilities, Assessment of Professional Practices Related to CDI Risk Prevention, and Strategies for Improving Care.
Clostridioides Difficile Infection
Active, not recruitingPhase 2
Autologous Fecal Microbiota Transplantation (Auto-FMT) for Prophylaxis of Clostridium Difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell
RecruitingPhase 3
A Study to Learn About a Clostridioides Difficile Vaccine in People 65 Years of Age and Older
Clostridoides Difficile Associated Disease
Active, not recruitingObservational study
C. Difficile Toxin Levels in Stool From Healthy Individuals Following Standard of Care Antibiotic Treatment for CDI.
Clostridioides Difficile Infection Recurrence
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections
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.
Julian A Abrams, MD, MS principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Omeprazole 40 mg bid in people with Clostridium Difficile, run by Daniel Freedberg, MD 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 2 inclusion and 11 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 15 Aug 2024. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Aug 2024). 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?
Shannon Diversity Index Measuring Change in Microbiome Diversity (time frame: Baseline (Week 0), Week 4, Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01901276, which also lists 1 linked publication.
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 Aug 2024.