Clinical trial NCT01680874: Probiotics for Clostridium Difficile Infection in Older Adults
Official title: A Pilot Study to Examine the Role of Probiotics for Improving Outcomes of C. Difficile
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridium Difficile
Keywords: Clostridium difficile
Diarrhea
Infection
Lactobacilli
Bifidobacteria
Lactobacillus acidophilus
Lactobacillus paracasei
Bifidobacterium lactis
Yogurt
Probiotics
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Aging (NIA)
First posted: 2012-09-07
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether a probiotic, when used together with standard treatment, is effective in reducing duration of symptoms and preventing recurrence of infection in older adults with a first episode of C. difficile infection.

Detailed description: 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 as adjunctive treatment of infections without the attendant risks of promoting antimicrobial resistance. Certain probiotics have demonstrated inhibition of adherence of pathogenic bacteria and stimulation of systemic immune functions, possibly enhancing the body's ability to eradicate C. difficile in the gastrointestinal tract. However, limited data is available on the efficacy of probiotics for ameliorating C. difficile symptoms and reducing recurrence of C. difficile infection (CDI). The investigators propose a pilot randomized, double-blind, placebo-controlled clinical trial in older adult inpatients with a first episode of CDI to evaluate the efficacy of a probiotic combination, in conjunction with standard treatment, for reducing duration of diarrhea and recurrence of CDI.

Eligibility criteria: Inclusion Criteria:

* Adult of either gender, 18 years or older with a first episode of C. difficile infection
* Meets the case definition of C. difficile infection-diarrhea associated with a positive stool test for C. difficile toxin(s) in the 2 days prior to enrollment treated with metronidazole or vancomycin

Exclusion Criteria:

* Severe disease defined as any of the following: WBC \> 30,000 or \< 1000 cells/mm\^3, elevated creatinine \> 1.5 times the premorbid level, ICU patient at time C. difficile infection diagnosed
* Has other known etiology of diarrhea (e.g. other enteric pathogen, other intestinal disease)
* Has a history of chronic intestinal disease (e.g. Crohn's disease, ulcerative colitis)
* Has a presence of toxic megacolon or ileus
* Has a presence of colostomy or nasogastric tube
* Has a history of abdominal surgery within the previous 3 months (from time of enrollment)
* Is enrolled in another investigational drug trial
* Is unavailable for follow-up visits
* History of multiple C. difficile infection
* Willing not to take other probiotics for duration of study
* Is severely immunocompromised.

Primary outcomes:
measure: Duration of diarrhea
timeFrame: 4 weeks
Secondary outcomes:
measure: Density of C. difficile toxin in stool
timeFrame: 8 weeks
measure: Stool cytokines
timeFrame: 8 weeks
measure: Fecal lactoferrin
timeFrame: 8 weeks
measure: Functional assessment using Barthel Index
timeFrame: 8 weeks
measure: Recurrence of CDI
timeFrame: 8 weeks
Other outcomes:
measure: Infection with Lactobacillus
timeFrame: 8 weeks
measure: Infection with Bifidobacterium
timeFrame: 8 weeks
Locations:
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin Department of Medicine (Infectious Disease)
name: Nasia Safdar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis. 2001 Jun 1;32(11):1567-76. doi: 10.1086/320518. Epub 2001 May 4.
citation: McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006 Apr;101(4):812-22. doi: 10.1111/j.1572-0241.2006.00465.x.
citation: Safdar N, Barigala R, Said A, McKinley L. Feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized US military veterans. J Clin Pharm Ther. 2008 Dec;33(6):663-8. doi: 10.1111/j.1365-2710.2008.00980.x.
citation: Barker AK, Duster M, Valentine S, Hess T, Archbald-Pannone L, Guerrant R, Safdar N. A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO). J Antimicrob Chemother. 2017 Nov 1;72(11):3177-3180. doi: 10.1093/jac/dkx254.
citation: Barker A, Duster M, Valentine S, Archbald-Pannone L, Guerrant R, Safdar N. Probiotics for Clostridium difficile infection in adults (PICO): Study protocol for a double-blind, randomized controlled trial. Contemp Clin Trials. 2015 Sep;44:26-32. doi: 10.1016/j.cct.2015.07.015. Epub 2015 Jul 22.