Probiotics Administration Via Colonoscopic Spray and Oral Administration in CDAD Patients (CDAD)

March 5, 2023 updated by: National Cheng-Kung University Hospital

The Comparison of the Adjuvant Effect of Probiotics Between Delivery Via Colonoscopic Spray and Oral Administration in Patients With Clostridioides Difficile Colitis Receiving Vancomycin Treatment

Clostridioides difficile (C. difficile) colitis is a common hospital-acquired disease, which increases hospitalization length and the mortality rate. Moreover, refractory or recurrent C. difficile colitis is an emerging disease. The tapering course of oral vancomycin or oral fidaxomicin is current standard treatment for refractory or recurrent C. difficile colitis. Fecal microbiota transplantation (FMT) is an alternative one. However, the tapering course of oral vancomycin needs a 6- to 12-week duration, fidaxomicin is expensive, and FMT is not available in every hospital; therefore, it is needed to develop a new treatment. Evidence has shown that the disturbance with reduced diversity of intestinal microbiota may lead to refractory C. difficile colitis. Besides fecal microbiota transplantation, probiotics administration can also correct the disturbed intestinal microbiota. However, inconsistent efficacy of probiotic administration was reported, which may be attributed to the interference by the gastric acid. Precise delivery of probiotics into the colon by colonoscopy can avoid the destruction by gastric acid, with which a better treatment efficacy is expected. The best regimen for C. difficile colitis should be the one which succeeds on the first attempt. Therefore, this study is aimed toward validating the efficacy and safety of the colonoscopic probiotics-spray.

Patients diagnosed with C. colitis will be enrolled. All patients will accept the standard treatment of oral vancomycin for 14 days. As an adjuvant probiotic administration at the same time, enrolled patients will be randomly assigned to the probiotics-spray (PS) group and the probiotics-oral (PO) group, respectively. The patients in the PS group will receive colonoscopic spray of probiotics once, while the patients in the PO group will receive the same dosage of oral probiotics divided into 5 days. This study will compare the difference in fecal microbiota changes between the colonoscopic probiotics-spray group and the probiotics-oral group. Moreover, this study will evaluate the efficacy and safety between the colonoscopic probiotics-spray and probiotics-oral in patients with C. difficile colitis.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Refractory or recurrent C. difficile colitis is an emerging disease. The tapering course of oral vancomycin or oral fidaxomicin is current standard treatment for refractory or recurrent C. difficile colitis.FMT is an alternative treatment. Nevertheless, the tapering course of oral vancomycin needs a 6- to 12-week duration, fidaxomicin is expensive, and FMT is not available in many hospitals. Therefore, we need a method which is effective for patients and available for clinicians.

The disturbance with reduced diversity of intestinal microbiota may lead to refractory or recurrent C. difficile colitis. Moreover, the probiotics administration can correct the disturbed intestinal microbiota. However, inconsistent efficacy of probiotic administration was reported, which may be attributed to the interference by the gastric acid. There is no exact estimation for the amounts of probiotics in the colon after oral administration. Moreover, there is no study which is conducted to compare the efficiency of probiotics between direct spray via colonoscopy and oral administration. It will be novel to study such issue. If the amounts of probiotics which is delivered directly via colonoscopy and the clinical efficacy are similar to those by FMT, colonoscopic probiotics-spray will replace FMT in clinical practice.

FMT can correct the disturbed intestinal microbiota. The estimated bacteria of human wet stool are 1011 per gram. The amount of stool for FMT is ~30 to 100 grams; thus, ~1012 to 1013 bacteria will be transplanted in an FMT procedure. In this project, we will transplant ~2x1011 probiotics into the colon by the colonoscopic spray. Therefore, we believe that colonoscopic spray of probiotics will have similar amounts of bacteria transplanted with FMT but be more efficient than oral probiotics administration.

Probiotics use may have adverse events. There are few studies and case reports which recorded that the administered probiotic was isolated from sterile sites, such as bacteremia. Thus, the safety issue of this study will focus on the adverse events, bacteremia and sepsis.

It will be novel to conduct the study to compare the efficacy and safety of probiotics which are delivered directly via colonoscopy and oral administration. If it works, colonoscopic probiotics spray will replace FMT in clinical practice.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • patients aged ≥ 20 years who are diagnosed with C. difficile colitis

Exclusion Criteria:

  • patients are diagnosed with colitis because of other etiologies, such as intestinal Behçet's disease, amoeba or parasitic colitis, Salmonella colitis, lymphoma, E. coli colitis, cytomegalovirus colitis, ischemic colitis, sigmoid-colon cancer, inflammatory bowel diseases (ulcerative colitis or Crohn's disease), solitary rectal ulcer syndrome, radiation colitis
  • patients who have contraindications for colonoscopy, including declining or refusal to cooperate
  • unstable vital signs
  • a diagnosis or highly suspicion of colon rupture
  • a high-risk situation for colon perforation such as acute diverticulitis
  • toxic megacolon, etc.
  • acute myocardial infarct

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: probiotics-spray (PS) group
In the PS group, the colonoscopic prescription of 10 grams of probiotics powder is performed once on one of the first three days (D0-D3).
Dietary supplement: Probiotics administration
A total of 10 grams of probiotics was administered in both group, but the routes were different. One group were per colonoscopic spray, and the other was per oral.
Active Comparator: probiotics-oral (PO) group
In the PO group, we will prescribe oral probiotics 2 capsules once per day for 5 days (a total of 10 grams) as adjunctive treatment during the first five days (D0-D4).
Dietary supplement: Probiotics administration
A total of 10 grams of probiotics was administered in both group, but the routes were different. One group were per colonoscopic spray, and the other was per oral.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The difference in fecal microbiota change, including probiotics, between the colonoscopic probiotics-spray and probiotics-oral and before and after probiotics use either by colonoscopic probiotics-spray or probiotics-oral
Time Frame: 5 days
All patients will be monitored for 30 days after diagnosis of C. difficile colitis. The primary endpoint is the comparison of the perseverance of fecal microbiota and metabolites. We will compare the microbiota by sequencing 16S rRNA, measured as percentage abundance per microbial species and differences in percentage abundance between the PS group and PO group in Day 0 and Day 5. We will also compare the relative abundance of C. difficile and target probiotics between the two study groups, such as Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus, or others.
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The resolution of C. difficile colitis
Time Frame: 30 days
the resolution time of diarrhea and bloody stool
30 days
Hospitalization length
Time Frame: 30 days
the total hospitalization length
30 days
Recurrence of C. difficile colitis
Time Frame: 30 days
the recurrence of C. difficile colitis
30 days
Mortality events
Time Frame: 30 days
all-cause mortality
30 days
Adverse events
Time Frame: 30 days
adverse events from probiotics, including probiotics bacteremia and sepsis
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cheng-Kung University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 21, 2023

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

March 5, 2023

First Submitted That Met QC Criteria

March 5, 2023

First Posted (Actual)

March 15, 2023

Study Record Updates

Last Update Posted (Actual)

March 15, 2023

Last Update Submitted That Met QC Criteria

March 5, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B-BR-111-052

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

IPD sharing after the study completed and the paper published

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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