Probiotic Lactobacillus GG to Eliminate VRE Colonization

Study Overview
=================
Brief Summary
-----------------
The use of LGG will be associated with elimination of VRE colonization. The primary comparison will be VRE elimination rates among those patients that receive LGG compared to those that receive placebo. The primary endpoint will be the proportion of patients with VRE at one week after cessation of administration of study medication or placebo. The investigators assume that the placebo group will have very little spontaneous elimination of VRE and that the LGG group will be more likely to have eliminated VRE colonization at the end of one week.

Official Title
-----------------
Probiotic Lactobacillus GG to Eliminate VRE Colonization

Conditions
-----------------
Vancomycin Resistant Enterococcal Colonization

Intervention / Treatment
-----------------
* Biological: Lactobacillus GG or Culturelle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater than or equal to 18 years Identified as having had a clinical isolate or stool or rectal swab culture positive for VRE Able to give informed consent and report on side effects Tolerating an oral/enteral diet Stable comorbid conditions Willing and able to come to Tufts for weekly visits Outpatient Exclusion Criteria: Inpatients Active infection with VRE being treated Pregnancy Known use of LGG or another probiotic (not including yogurt) within the previous 30 days Presence of an active bowel leak, acute abdomen, active intestinal disease, or significant bowel dysfunction Presence of an absolute neutrophil count less than 500 per cubic mm or anticipation post chemotherapy that the absolute neutrophil count will fall below 500 per cubic mm History of adverse reaction to product containing lactobacillus Active colitis (see definition below) Treatment with an antibiotic with activity against VRE Life expectancy less than one year or life-threatening condition Known or suspected allergies to probiotics, lactobacillus, milk protein, and microcrystalline cellulose Structural heart disease, history of endocarditis or valve replacement Positive baseline stool culture for LGG Recent or planned chemotherapy or radiation therapy Solid organ transplant within the prior year Stem cell transplant within the prior year On active immunosuppressive medication [anti-rejection, injectable immunosuppressive drugs for autoimmune disease, or corticosteroids (greater than 1/2 mg per kg body weight of prednisone or its equivalent) not including inhaled or topical steroids] Allergy or intolerance to or contraindication to two or more of the rescue antibiotic regimens (ampicillin, clindamycin, moxifloxacin) Colitis will be defined as a history of Crohn's disease or ulcerative colitis with active diarrhea, active diarrhea due to Clostridium difficile infection, active diarrhea due to known or unknown cause with a stool specimen showing fecal leukocytes (if none has been done in such a patient this will be requested prior to enrollment). Diarrhea will be defined as more than three unformed bowel movements per day. The subject's primary physician will be asked to assess the subject's life expectancy, and subjects with an estimated life expectancy of less than one year as judged by the physician who knows him or her best will be excluded.

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 |
| --- | --- |
| Active Comparator: 1<br>Lactobacillus rhamnosus LGG | Biological: Lactobacillus GG or Culturelle<br>* Drug to be administered orally (capsule form). Dose=2 capsules/day for 14 days. Dosage strength= 1x10^10 bacteria<br>* Other names: Placebo is microcrystalline cellulose;|
| Placebo Comparator: 2<br>Microcrystalline cellulose capsules | Biological: Lactobacillus GG or Culturelle<br>* Drug to be administered orally (capsule form). Dose=2 capsules/day for 14 days. Dosage strength= 1x10^10 bacteria<br>* Other names: Placebo is microcrystalline cellulose;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint will be the proportion of patients with VRE at one week after cessation of administration of study medication or placebo. |  | Day 21post enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of VRE colonization in LGG recipients versus controls at 2 weeks and 6 weeks post discontinuation of administration of LGG or placebo. |  | 2 weeks, and 6 weeks | 
| The rate of LGG colonization in study population receiving LGG compared to placebo. |  | days 21, 28, 56 | 
| That LGG can be used safely and without significant side effects in both hospitalized and ambulatory patients. |  | day 0-56 and 6 mnths | 
| That among those treated with LGG, the colony counts of VRE will be lower when compared to controls even among those in whom colonization is not eliminated. |  | day 0,7,14,21,28,56 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vancomycin Resistant enterococcal colonization, Probiotics, Lactobacillus rhamnosus, LGG