Probiotics for Clostridium Difficile Infection in Older Adults

Study Overview
=================
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.

Official Title
-----------------
A Pilot Study to Examine the Role of Probiotics for Improving Outcomes of C. Difficile

Conditions
-----------------
Clostridium Difficile

Intervention / Treatment
-----------------
* Dietary Supplement: Probiotic
* Dietary Supplement: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>This arm will receive a probiotic combination which will consist of equal amounts of Lactobacillus acidophilus NCFM® (ATCC 700396), Lactobacillus paracasei Lpc-37 (ATCC SD5275), Bifidobacterium lactis Bi-07 (ATCC SC5220), and Bifidobacterium lactis Bl-04 (ATCC SD5219). The probiotic will be taken orally, once a week, for 4 weeks. | Dietary Supplement: Probiotic<br>* The intervention will consist of the subject taking the study medication once a day for 4 weeks. During hospitalization, patients will be followed daily for diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. Upon discharge from the hospital, patients will be contacted through weekly phone calls to assess diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. At weeks 4 and 8, a stool sample will be collected, and the stool diary will be reviewed.<br>* Other names: ATCC SD5219;|
| Placebo Comparator: Placebo<br>A placebo will be taken orally, once a day, for 4 weeks. | Dietary Supplement: Placebo<br>* The intervention will consist of the subject taking the placebo once a day for 4 weeks. day for 4 weeks. During hospitalization, patients will be followed daily for diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. Upon discharge from the hospital, patients will be contacted through weekly phone calls to assess diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. At weeks 4 and 8, a stool sample will be collected, and the stool diary will be reviewed.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of diarrhea | Duration of diarrhea, as indicated by a stool diary kept by the patient | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Density of C. difficile toxin in stool |  | 8 weeks | 
| Stool cytokines |  | 8 weeks | 
| Fecal lactoferrin |  | 8 weeks | 
| Functional assessment using Barthel Index |  | 8 weeks | 
| Recurrence of CDI | Diagnosis with a recurrent episode of C. difficile infection | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Yogurt, Clostridium difficile, Diarrhea, Infection, Lactobacilli, Bifidobacteria, Lactobacillus acidophilus, Lactobacillus paracasei, Bifidobacterium lactis, Probiotics