Impact of Probiotics for Reducing Infections in Veterans: The IMPROVE Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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IMpact of PRObiotics for Reducing Infections in VEterans: The IMPROVE Study

Conditions
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Anti-biotic Resistance

Intervention / Treatment
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* Dietary Supplement: Lactobacillus rhamnosus HN001
* Dietary Supplement: sugar pill (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Probiotic<br>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 | Dietary Supplement: Lactobacillus rhamnosus HN001<br>* 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<br>|
| Placebo Comparator: Arm 2: Placebo<br>Placebo identical to the active product will be given | Dietary Supplement: sugar pill (placebo)<br>* Placebo identical to the active product will be given<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infection, probiotics