Clinical trial NCT01321606: Impact of Probiotics for Reducing Infections in Veterans: The IMPROVE Study
Official title: IMpact of PRObiotics for Reducing Infections in VEterans: The IMPROVE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anti-biotic Resistance
Keywords: infection
probiotics
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University of Wisconsin, Madison
First posted: 2011-03-23
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Oral L. Rhamnosus HN001 Therapy Compared to Placebo on Gastrointestinal and Extra-gastrointestinal Colonization of S. Aureus.
timeFrame: 4 weeks
Secondary outcomes:
measure: Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
timeFrame: 4 weeks
measure: Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Madison
country: United States
facility: William S. Middleton Memorial Veterans Hospital, Madison, WI
state: Wisconsin
Study officials:
affiliation: William S. Middleton Memorial Veterans Hospital, Madison, WI
name: Nasia Safdar, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Eggers 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.