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

NCT ID: NCT01321606

Last Updated: 2018-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 113 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2015-12-31

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.

Conditions

Anti-biotic Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Arm 1: Probiotic

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

Group Type: EXPERIMENTAL

Lactobacillus rhamnosus HN001

Intervention Type: DIETARY_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

Arm 2: Placebo

Placebo identical to the active product will be given

Group Type: PLACEBO_COMPARATOR

sugar pill (placebo)

Intervention Type: DIETARY_SUPPLEMENT

Placebo identical to the active product will be given

Interventions

Lactobacillus rhamnosus HN001

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

Intervention Type: DIETARY_SUPPLEMENT

sugar pill (placebo)

Placebo identical to the active product will be given

Intervention Type: DIETARY_SUPPLEMENT

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nasia Safdar, MD PhD

Role: PRINCIPAL_INVESTIGATOR

William S. Middleton Memorial Veterans Hospital, Madison, WI

Locations

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29540160 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27836508 (View on PubMed)

Other Identifiers

OMB 4040-0001

Identifier Type: OTHER

Identifier Source: secondary_id

CLIN-010-10S

Identifier Type: -

Identifier Source: org_study_id