Support of Colonization Resistance of the Gut Microbiota With the Synbiotic Food Supplement Nagasin®

Randomized, Controlled, Double-blind, Parallel, Multicentric Study to Investigate Support of the Colonization Resistance of the Gut Microbiota With the Synbiotic Food Supplement Nagasin® After Disturbance by Antimicrobial Treatment

The aim of this randomized, controlled, double-blind, parallel, multicentric trial is to investigate wether the synbiotic food supplement Nagasin® can support the colonization resistance of the gut microbiota after disturbance by antimicrobial treatment.

The main question is whether Nagasin® can prevent any increase in abundance of C.difficile within the first four weeks after antimicrobial treatment for a C. difficile infection.

Participants will receive Nagasin® or the comparator as a food supplement during the first four weeks after antimicrobial treatment for a C. difficile episode.

Study Overview

• Status: Recruiting
• Conditions: C. Difficile Enteritis
• Intervention / Treatment: Dietary supplement: Nagasin; Dietary supplement: maltodextrin

• Study Type: Interventional
• Enrollment (Estimated): 147
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Isabelle M Frey-Wagner, PhD; Phone Number: +41 76 426 33 10; Email: isabelle.frey@imm.uzh.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital Bern
    • Contact: Benjamin Misselwitz; Phone Number: +41 31 664 04 30; Email: benjamin.misselwitz@insel.ch
  • BL
    • Liestal, BL, Switzerland, 4410
      • Not yet recruiting
      • Kantonsspital Baselland
      • Contact: Emanuel Burri, MD
  • LU
    • Luzern, LU, Switzerland, 6000
      • Not yet recruiting
      • Luzerner Kantonsspital
      • Contact: Simon Bütikofer, MD
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich
      • Contact: Luc Biedermann, MD; Phone Number: + 41 44 255 11 11; Email: luc.biedermann@usz.ch
    • Zürich, ZH, Switzerland, 8063
      • Not yet recruiting
      • Stadtspital Zürich
      • Contact: Bernhard Morell, MD
  • Zurich
    • Winterthur, Zurich, Switzerland, 8400
      • Recruiting
      • Kantonsspital Winterthur
      • Contact: Michael Osthoff, MD; Phone Number: +41 52 266 2757; Email: michael.osthoff@ksw.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• C. difficile infection diagnosis
• antimicrobial treatment (e.g. metronidazole, vancomycin or fidaxomicin) for C. difficile infection at ICF
• Written informed consent by the participant after information about the research project

Exclusion Criteria:

• total parenteral nutrition
• insulin-dependent (type 1) diabetes

• severe disease defined as any of the following:

  • WBC > 30,000 or < 1000 cells/mm3
  • Neutropenia < 500 x 10^9 per liter
  • ICU patient at time C. difficile infection diagnosed
  • In case no hematology values are available, presence of severe can be evaluated by the local principal investigator or his designee

• is severely immunocompromised as defined by any of the following:

  • active malignancy receiving severe immunosuppressive chemotherapy with subsequent leukopenia (as defined above)
  • long-term systemic steroid therapy ≥ 30 mg / d
  • recipients of stem cell transfer (≤ 12 months)
  • severe inborne immune deficiency or severe immunosuppressive therapy as evaluated by the investigator
  • HIV patients with low CD4+ cell count (< 200 x 10^9 per liter)
  • Inflammatory bowel disease patients if:
  • severe ulcerative colitis (classified as endoscopic Mayo = 3 (max. 30 days old) or as evaluated by investigator)
  • Severe Crohn's disease with acute penetrating complication (abscess and/or actively draining fistulae) or as evaluated by investigator
  • Liver cirrhosis (classified as Child C) with clinically significant portal hypertension and/or low thrombocyte count (20 × 10^9 per liter)
• Acute pancreatitis
• prosthetic heart valves or endocarditis
• consumption of other high-dose (>10^10 cfu/dose) probiotic products during the study period.
• Inability to understand and follow study procedures
• prosthetic heart valves or endocarditis
• consumption of other high-dose (>10^10 cfu/dose) probiotic products during the study period.
• Inability to understand and follow study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nagasin®; consumption of Nagasin® (synbiotic food supplement) once per day for four weeks	Dietary supplement: Nagasin; Lactobacillus, Lactococcus and Bifidobacteria strains with antimicrobial effect against C. difficile
Placebo Comparator: Comparator; consumption of the comparator (maltodextrin) once per day for four weeks	Dietary supplement: maltodextrin; maltodextrin (placebo comparator)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C. difficile relative abundance	any change of C. difficile relative abundance during the first four weeks after antimicrobial treatment for CDI.	at 1, 2 and 4 weeks after completion of antimicrobial treatment for CDI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota	Gut microbiota diversity and taxonomic composition	at 1, 2, 4 and 8 weeks after completion of antimicrobial treatment for CDI
Abundance of antibiotic diarrhea associated pathogens	Abundance of other pathogens that are involved in antibiotic associated diarrhea e.g. S. aureus and K. oxytoca	at 1, 2, 4 and 8 weeks after completion of antimicrobial treatment for CDI
C. difficile toxins	Presence and amount of C. difficile toxins	at 1, 2, 4 and 8 weeks after completion of antimicrobial treatment for CDI
Toxin forming C. difficile strains	Presence of toxin forming C. difficile strains	at 1, 2, 4 and 8 weeks after completion of antimicrobial treatment for CDI

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Luzerner Kantonsspital; Kantonsspital Winterthur KSW; Cantonal Hosptal, Baselland; Insel Gruppe AG, University Hospital Bern; Stadtspital Zürich
• Investigators: Study Chair: Isabelle M Frey-Wagner, PhD, University or Zurich, Institute of Medical Microbiology

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 20, 2024

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Gut microbiota; Colonization resistance; Gut microbiota dysbiosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enteritis
• Other Study ID Numbers: BASEC 2022-01318

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No