Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Investigation of the Optimal Cocktailed Probiotics for Decolonization of Vancomycin-resistant Enterococci in Human Gut

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03822819
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : February 28, 2019
Sponsor:
Collaborators:
Taipei Medical University
Delta Electronics
Information provided by (Responsible Party):
Taipei Medical University Shuang Ho Hospital

Brief Summary:
Vancomycin-resistant enterococci (VRE) has been a serious public health issue as an opportunistic pathogen and reservoir of antibiotic resistant genes. To reduce VRE carriage in human gut, investigators aim to look for effective probiotic cocktail to compete with VRE in human gut microflora via the technique of microbiome analysis pipeline (MAP). The probiotic cocktail gave by MAP result will be tested in a clinical trial, in which 80 subjects with VRE carriage will be enrolled and allocated randomly into two groups. Subjects in first group will be administered with probiotic cocktail capsules, and placebo capsules will be given to the second group in a double-blind manner. Stool samples will be collected from subjects before and after three weeks of probiotic/probiotic capsule uptake, and analyzed for VRE number and gut microflora changes to evaluate the efficacy of probiotic cocktail.

Condition or disease Intervention/treatment Phase
Vancomycin-Resistant Enterococci Probiotics Dietary Supplement: probiotic cocktail capsules Dietary Supplement: placebo capsules Not Applicable

Detailed Description:

Enterococci are one of the commensal gut flora in humans and have become an important pathogenic bacterium of opportunistic infection. Enterococci can cause severe infection when the patients become immunocompromised and subsequent serious problem in medical therapy because last line antibiotics could be ineffective. The incidences of vancomycin-resistant enterococci (VRE) have been increasing all over the world in recent years. VRE have become a global threat in human health and medical care because of the possible spreading of antibiotic resistance genes. So far probiotic bacteria have played various important roles in regulation of gut functions and some positive impact on diabetes, liver function impairment, and psychiatric disorders. Recently a few probiotic studies indicated that VRE could possibly be decolonized from human gut. However, it remains controversial because of different probiotic strains, dosages, durations of administrations, and study designs in these reports. Therefore, further in vitro studies and clinical trials are warranted for validation of the hypothesis that VRE could be decolonized by probiotic bacteria from human gut.

In the preliminary study using Microbiome analysis pipeline to dissect the NGS (next generation sequencing) data from the co-cultures of two VRE strains (Enterococcus faecium, Enterococcus faecalis) and ten TFDA (Taiwan Food and Drug Administration)-approved probiotic bacteria, investigators have confirmed that the mixture of the ten probiotic bacteria significantly suppressed the bacterial amounts of VRE during the in vitro co-cultures. The results will provide a formula of optimal cocktailed probiotics in which a specific combination of the selected probiotic bacteria could exert a maximal effect on suppression of growth of VRE.

First, An in vitro co-culture of VRE and the optimal cocktailed probiotics selected by Microbiome analysis pipeline will be conducted for validation of the results from the preliminary study. Gastric acid-resistant capsules containing the probiotic cocktail validated with in vitro co-culture model, will then be prepared in dosage of 10^10 CFU (Colony Forming Unit).

Second, in the proposed clinical trial, participants of age between 20 and 80-year-old will be selected and admitted to Taipei Medical University Hospital with isolated vancomycin-resistance enterococci (VRE) from their stools after hospitalization. Exclusion criteria in this study are individuals: (1) with routine probiotic uptake in daily life, or being prescribed with probiotics in clinic one-week before or in the period of clinical trial; (2) being prescribed with oral antibiotic uptake in the period of clinical trial; (3) with diarrhea symptom; (4) in pregnancy; (5) of immuno-compromised conditions or being prescribed with steroid-type medicines; (6) with diabetes mellitus; (7) critically ill patients.

When the conditions of their underlying diseases are stabilized, these patients who sign the informed consents will be randomly assigned into two groups receiving the cocktailed probiotics or placebo for 3 weeks in double-blind masking. The stool samples will be collected before and after the 3-week administration of the cocktailed probiotics or placebo. After completion of enrolling 80 patients in total umber, the double-blinded capsules will be unlabeled and at least 50 patients with 25 completed paired stool samples in both groups will be further processed for genomic DNA isolation and 16s rDNA (ribosomal DNA) NGS analysis. Finally, the quantities of VRE in stool samples will be analyzed with colony formation number on selective medium, and alterations of gut microbiota will be analyzed through stool microbiome 16s rDNA NGS. The results will be compared between the cocktailed probiotics group and the placebo group for evaluation of the VRE decolonization effect of probiotics.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study is going to be carried out with two groups in which participants are either administered with probiotic cocktail capsules or placebo capsules
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigation of the Optimal Cocktailed Probiotics for Decolonization of Vancomycin-resistant Enterococci in Human Gut
Estimated Study Start Date : March 4, 2019
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Vancomycin

Arm Intervention/treatment
Experimental: probiotic cocktail capsules uptake
Participants take two capsules of probiotic cocktail everyday for 30 days in a double-blinded masking. Stool samples will be collected before and after capsule uptake and be analyzed for VRE number and microbiota change.
Dietary Supplement: probiotic cocktail capsules
Daily uptake of probiotic cocktail for three weeks

Placebo Comparator: placebo capsules uptake
Participants take two capsules of placebo everyday for 30 days in a double-blinded masking. Stool samples will be collected before and after capsule uptake and be analyzed for VRE number and microbiota change.
Dietary Supplement: placebo capsules
Daily uptake of placebo capsule for three weeks




Primary Outcome Measures :
  1. VRE number change [ Time Frame: after 30 days of capsules uptake ]
    Stool samples will be collected from participants before and after capsule uptake and plating out on selective medium for VRE after proper serial dilution. VRE number is defined as VRE CFU per gram of stool sample, and compared between two samples from the same participant.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • VRE-carriage
  • of age between 20 and 80-year-old
  • agreeing to participate

Exclusion Criteria:

  • routine probiotic uptake in daily life, or being prescribed with probiotics in clinic one- week before or in the period of clinical trial
  • being prescribed with oral antibiotic uptake in the period of clinical trial
  • with diarrhea symptom
  • in pregnancy
  • of immuno-compromised conditions or being prescribed with steroid-type medicines
  • with diabetes mellitus
  • critically ill patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03822819


Contacts
Layout table for location contacts
Contact: Shiuh-Bin Fang, M.D, Ph.D. +886 2 22490088 ext 2955 sbfang@tmu.edu.tw

Locations
Layout table for location information
Taiwan
Taipei Medical University Hospital Recruiting
Taipei, Taiwan, 110
Contact: Yuarn-Jang Lee, M.D.    +886 2 27372181 ext 3979    yuarn438@yahoo.com.tw   
Sponsors and Collaborators
Taipei Medical University Shuang Ho Hospital
Taipei Medical University
Delta Electronics
Investigators
Layout table for investigator information
Principal Investigator: Shiuh-Bin Shiuh-Bin, M.D, Ph.D. Taipei Medical University-ShuangHo Hospital

Layout table for additonal information
Responsible Party: Taipei Medical University Shuang Ho Hospital
ClinicalTrials.gov Identifier: NCT03822819     History of Changes
Other Study ID Numbers: N201805035
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents