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Probiotics for Clostridium Difficile Infection in Older Adults (PICO)

Primary Purpose

Clostridium Difficile

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Probiotic

Placebo

About this trial

This is an interventional treatment trial for Clostridium Difficile focused on measuring Clostridium difficile, Diarrhea, Infection, Lactobacilli, Bifidobacteria, Lactobacillus acidophilus, Lactobacillus paracasei, Bifidobacterium lactis, Yogurt, Probiotics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Wisconsin Hospital and Clinics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Probiotic

Placebo

Arm Description

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.

A placebo will be taken orally, once a day, for 4 weeks.

Outcomes

Primary Outcome Measures

Duration of diarrhea

Duration of diarrhea, as indicated by a stool diary kept by the patient

Secondary Outcome Measures

Density of C. difficile toxin in stool

Stool cytokines

Fecal lactoferrin

Functional assessment using Barthel Index

Recurrence of CDI

Diagnosis with a recurrent episode of C. difficile infection

Full Information

NCT ID

NCT01680874

First Posted

September 4, 2012

Last Updated

December 1, 2015

Sponsor

University of Wisconsin, Madison

Collaborators

National Institutes of Health (NIH), National Institute on Aging (NIA)

1. Study Identification

Unique Protocol Identification Number

NCT01680874

Brief Title

Probiotics for Clostridium Difficile Infection in Older Adults

Acronym

PICO

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

February 2013 (undefined)

Primary Completion Date

February 2015 (Actual)

Study Completion Date

February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Wisconsin, Madison

Collaborators

National Institutes of Health (NIH), National Institute on Aging (NIA)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clostridium Difficile

Keywords

Clostridium difficile, Diarrhea, Infection, Lactobacilli, Bifidobacteria, Lactobacillus acidophilus, Lactobacillus paracasei, Bifidobacterium lactis, Yogurt, Probiotics

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Probiotic

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

A placebo will be taken orally, once a day, for 4 weeks.

Intervention Type

Dietary Supplement

Intervention Name(s)

Probiotic

Other Intervention Name(s)

Lactobacillus acidophilus NCFM®, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bi-07, Bifidobacterium lactis Bl-04, ATCC 700396, ATCC SD5275, ATCC SD5220, ATCC SD5219

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Duration of diarrhea

Description

Duration of diarrhea, as indicated by a stool diary kept by the patient

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Density of C. difficile toxin in stool

Time Frame

8 weeks

Title

Stool cytokines

Time Frame

8 weeks

Title

Fecal lactoferrin

Time Frame

8 weeks

Title

Functional assessment using Barthel Index

Time Frame

8 weeks

Title

Recurrence of CDI

Description

Diagnosis with a recurrent episode of C. difficile infection

Time Frame

8 weeks

Other Pre-specified Outcome Measures:

Title

Infection with Lactobacillus

Description

Fever and other signs of infection with Lactobacillus, and infection confirmed through blood cultures

Time Frame

8 weeks

Title

Infection with Bifidobacterium

Description

Fever and other signs of infection with Bifidobacterium, and infection confirmed through blood cultures

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nasia Safdar, MD

Organizational Affiliation

University of Wisconsin Department of Medicine (Infectious Disease)

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Wisconsin Hospital and Clinics

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

11340528

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.

Results Reference

background

PubMed Identifier

16635227

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.

Results Reference

background

PubMed Identifier

19138244

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.

Results Reference

background

PubMed Identifier

28961980

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.

Results Reference

derived

PubMed Identifier

26210512

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.

Results Reference

derived

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Probiotics for Clostridium Difficile Infection in Older Adults

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