Anti-biotic ResistancePhase 2NCT01321606
Impact of Probiotics for Reducing Infections in Veterans: The IMPROVE Study
A Phase 2 study testing Lactobacillus rhamnosus HN001 in people with Anti-biotic Resistance, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The investigators have two hypotheses: (1) The probiotic L. rhamnosus HN001, when compared to placebo, will reduce S. aureus nasal colonization when taken for four weeks. (2) The probiotic L. rhamnosus HN001, when compared to placebo, will reduce S. aureus gastrointestinal colonization when taken for four weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anti-biotic Resistance
- What is being tested?
- Lactobacillus rhamnosus HN001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 113 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Dec 2015
- Phase
- Phase 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
- Colonized at nasal or gastrointestinal source by S. aureus including MRSA
- Age 18 years or older
- Able to take oral medications
- Able to provide informed consent
Who cannot join
- Uncontrolled psychiatric illness
- On a decolonization protocol for MRSA (e.g mupirocin, tea tree oil)
- Current involvement in another investigational trial
- Pregnancy
- Persistent diarrhea (> 3 loose stools per day for at least 2 days)
- Active infection with S.aureus or MRSA
Trial locations and contacts
1 site in 1 country.
United States1 site
William S. Middleton Memorial Veterans Hospital, Madison, WI
Madison, Wisconsin, 53705
About this study
Official title: IMpact of PRObiotics for Reducing Infections in VEterans: The IMPROVE Study
The investigators have two hypotheses: (1) The probiotic L. rhamnosus HN001, when compared to placebo, will reduce S. aureus nasal colonization when taken for four weeks. (2) The probiotic L. rhamnosus HN001, when compared to placebo, will reduce S. aureus gastrointestinal colonization when taken for four weeks.
Read the detailed description
Reducing infections caused by S. aureus is essential. The knowledge that colonization at a few key body sites such as the nose and the gastrointestinal tract is a prerequisite for infection2 ,3 offers an opportunity for therapeutic intervention. Thirty percent of the population has nasal colonization with S. aureus. In the last few years, decolonization agents such as mupirocin topical ointment and oral antibiotics such as doxycycline and rifampin have been studied for their utility in reducing colonization. However, these options have limitations in that recolonization is common, the impact of these interventions on multiple sites of colonization has not been assessed and resistance develops frequently to any of these, especially the oral antibiotics. Resistance in S. aureus has been designated a public health crisis. Methicillin-resistant S. aureus (MRSA) now accounts for 60% of all S. aureus infections. As an example of the growing crisis in S. aureus resistance, it should be noted that the number of MRSA infections rose from 2000 in 1993 to 368,000 in 2005. MRSA infections pose an even greater health and economic burden on the population than those caused by methicillin-sensitive S. aureus.4-8 S. aureus and MRSA infection trends in the VA health system mirror national trends5 and are associated with considerable morbidity and mortality in Veterans. A treatment that reduces S. aureus and MRSA colonization, without a risk of promoting antibiotic resistance could represent a breakthrough in decolonization therapy. Probiotics may be one such treatment option.
Probiotics are live microorganisms that are available over the counter, widely used as dietary supplements or nutritional foods and represent a low-cost, well tolerated, safe, non-antibiotic based strategy that may have efficacy for decolonization without the attendant risks of promoting antimicrobial resistance.9 Certain probiotics, including Lactobacillus rhamnosus HN001, have demonstrated ability to stimulate systemic immune functions, possibly enhancing the body's ability to eradicate S. aureus in the gastrointestinal tract and at sites remote from the gastrointestinal tract such as the nose.10 ,11 The long-term goal of this research is to identify and test novel interventions for reducing infections caused by resistant bacteria. The investigators propose a Phase II randomized, double-blind, placebo-controlled clinical trial in Veterans to evaluate the efficacy of an oral probiotic, Lactobacillus rhamnosus HN001, for reducing S. aureus colonization. This study will produce data, methods, and tools that have widespread relevance and portability, with the potential to reduce healthcare-associated infections.
- Conditions
- Anti-biotic Resistance
- Being tested
- Lactobacillus rhamnosus HN001, sugar pill (placebo)
- Keywords
- infection, probiotics
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus rhamnosus HN001Dietary supplement
Subjects will be given a pill formulation of a probiotic L. rhamnosus HN001 to be taken once a day, at a dose of 1 x 10^10 organisms
sugar pill (placebo)Dietary supplement
Placebo identical to the active product will be given
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Probiotic | Experimental | subjects will be given a capsule formulation of a 1x10^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks Receives: Dietary Supplement: Lactobacillus rhamnosus HN001 |
| Arm 2: Placebo | Placebo comparator | Placebo identical to the active product will be given Receives: Dietary Supplement: sugar pill (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral L. Rhamnosus HN001 Therapy Compared to Placebo on Gastrointestinal and Extra-gastrointestinal Colonization of S. Aureus.
Participants in the final outcome may be colonized at both GI and Extra-GI sites, thus the total numbers from the outcome cells can be greater than the overall number of participants analyzed.
Measured: 4 weeks
Secondary outcomes (2)
Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
This outcome is the mean difference in the % of granulocytes that phagocytized E. coli, from blood samples taken at the beginning and end of the trial. Percent of granulocytes phagocytizing E. coli at baseline is subtracted by percent of granulocytes phagocytizing E. coli at the end of the trial. The mean and standard error are calculated and reported for each study arm. This result
Measured: 4 weeks
Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
This outcome is the mean difference in the % of monocytes that phagocytized E. coli, from blood samples taken at the beginning and end of the trial. Percent of monocytes phagocytizing E. coli at baseline is subtracted by percent of monocytes phagocytizing E. coli at the end of the trial. The mean and standard error are calculated and reported for each study arm.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2011 (estimated)
- Study startOct 2011
- Primary completionDec 2015
- Study completionDec 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 (2)Papers the sponsor has linked to this study.
- Other trials for Anti-biotic ResistanceStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of Wisconsin, Madison
- Responsible party
- Sponsor
- Investigators
- Nasia Safdar, MD PhD, Principal investigator, William S. Middleton Memorial Veterans Hospital, Madison, WI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01321606
- Sponsor's protocol ID
- CLIN-010-10S
- Other IDs
- OMB 4040-0001
- Status last verified
- Nov 2017
- First submitted
- 21 Mar 2011
- Last updated
- 3 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Eggers S, Barker AK, Valentine S, Hess T, Duster M, Safdar N. Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study. BMC Infect Dis. 2018 Mar 14;18(1):129. doi: 10.1186/s12879-018-3028-6.
PubMed 29540160Eggers S, Barker A, Valentine S, Hess T, Duster M, Safdar N. Impact of Probiotics for Reducing Infections in Veterans (IMPROVE): Study protocol for a double-blind, randomized controlled trial to reduce carriage of Staphylococcus aureus. Contemp Clin Trials. 2017 Jan;52:39-45. doi: 10.1016/j.cct.2016.11.004. Epub 2016 Nov 9.
PubMed 27836508
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMpact of PRObiotics for Reducing Infections in VEterans: The IMPROVE Study
- ClinicalTrials.gov ID
- NCT01321606
- Acronym / sponsor ID
- CLIN-010-10S
- Conditions
- Anti-biotic Resistance
- Keywords
- infection, probiotics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of Wisconsin, Madison
- Study start
- Oct 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 23 Mar 2011 (estimated)
- Results
- Posted 3 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators have two hypotheses: (1) The probiotic L. rhamnosus HN001, when compared to placebo, will reduce S. aureus nasal colonization when taken for four weeks. (2) The probiotic L. rhamnosus HN001, when compared to placebo, will reduce S. aureus gastrointestinal colonization when taken for four weeks.
Detailed description
Reducing infections caused by S. aureus is essential. The knowledge that colonization at a few key body sites such as the nose and the gastrointestinal tract is a prerequisite for infection2 ,3 offers an opportunity for therapeutic intervention. Thirty percent of the population has nasal colonization with S. aureus. In the last few years, decolonization agents such as mupirocin topical ointment and oral antibiotics such as doxycycline and rifampin have been studied for their utility in reducing colonization. However, these options have limitations in that recolonization is common, the impact of these interventions on multiple sites of colonization has not been assessed and resistance develops frequently to any of these, especially the oral antibiotics. Resistance in S. aureus has been designated a public health crisis. Methicillin-resistant S. aureus (MRSA) now accounts for 60% of all S. aureus infections. As an example of the growing crisis in S. aureus resistance, it should be noted that the number of MRSA infections rose from 2000 in 1993 to 368,000 in 2005. MRSA infections pose an even greater health and economic burden on the population than those caused by methicillin-sensitive S. aureus.4-8 S. aureus and MRSA infection trends in the VA health system mirror national trends5 and are associated with considerable morbidity and mortality in Veterans. A treatment that reduces S. aureus and MRSA colonization, without a risk of promoting antibiotic resistance could represent a breakthrough in decolonization therapy. Probiotics may be one such treatment option.
Probiotics are live microorganisms that are available over the counter, widely used as dietary supplements or nutritional foods and represent a low-cost, well tolerated, safe, non-antibiotic based strategy that may have efficacy for decolonization without the attendant risks of promoting antimicrobial resistance.9 Certain probiotics, including Lactobacillus rhamnosus HN001, have demonstrated ability to stimulate systemic immune functions, possibly enhancing the body's ability to eradicate S. aureus in the gastrointestinal tract and at sites remote from the gastrointestinal tract such as the nose.10 ,11 The long-term goal of this research is to identify and test novel interventions for reducing infections caused by resistant bacteria. The investigators propose a Phase II randomized, double-blind, placebo-controlled clinical trial in Veterans to evaluate the efficacy of an oral probiotic, Lactobacillus rhamnosus HN001, for reducing S. aureus colonization. This study will produce data, methods, and tools that have widespread relevance and portability, with the potential to reduce healthcare-associated infections.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Probiotic | Experimental | Dietary Supplement: Lactobacillus rhamnosus HN001subjects will be given a capsule formulation of a 1x10^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks |
| Arm 2: Placebo | Placebo comparator | Dietary Supplement: sugar pill (placebo)Placebo identical to the active product will be given |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Colonized at nasal or gastrointestinal source by S. aureus including MRSA
- Age 18 years or older
- Able to take oral medications
- Able to provide informed consent
Key exclusion criteria (6 listed)
- Uncontrolled psychiatric illness
- On a decolonization protocol for MRSA (e.g mupirocin, tea tree oil)
- Current involvement in another investigational trial
- Pregnancy
- Persistent diarrhea (> 3 loose stools per day for at least 2 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 |
|---|---|---|
| Lactobacillus rhamnosus HN001Subjects will be given a pill formulation of a probiotic L. rhamnosus HN001 to be taken once a day, at a dose of 1 x 10^10 organisms | Dietary supplement | Arm 1: Probiotic |
| sugar pill (placebo)Placebo identical to the active product will be given | Dietary supplement | Arm 2: Placebo |
Primary outcome
Oral L. Rhamnosus HN001 Therapy Compared to Placebo on Gastrointestinal and Extra-gastrointestinal Colonization of S. Aureus.
Time frame: 4 weeks
Participants in the final outcome may be colonized at both GI and Extra-GI sites, thus the total numbers from the outcome cells can be greater than the overall number of participants analyzed.
2 secondary outcomes
Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
Time frame: 4 weeks
Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29540160Eggers S, Barker AK, Valentine S, Hess T, Duster M, Safdar N. Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study. BMC Infect Dis. 2018 Mar 14;18(1):129. doi: 10.1186/s12879-018-3028-6.
- Derived from this study: PubMed 27836508Eggers S, Barker A, Valentine S, Hess T, Duster M, Safdar N. Impact of Probiotics for Reducing Infections in Veterans (IMPROVE): Study protocol for a double-blind, randomized controlled trial to reduce carriage of Staphylococcus aureus. Contemp Clin Trials. 2017 Jan;52:39-45. doi: 10.1016/j.cct.2016.11.004. Epub 2016 Nov 9.
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.
Nasia Safdar, MD PhD principal investigator
William S. Middleton Memorial Veterans Hospital, Madison, WI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lactobacillus rhamnosus HN001 in people with Anti-biotic Resistance, run by VA Office of Research and Development 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 4 inclusion and 6 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 3 Aug 2018. 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 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 3 Aug 2018). 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?
Oral L. Rhamnosus HN001 Therapy Compared to Placebo on Gastrointestinal and Extra-gastrointestinal Colonization of S. Aureus. (time frame: 4 weeks). 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 NCT01321606, which also lists 2 linked publications.
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 3 Aug 2018.