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Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission

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ClinicalTrials.gov Identifier: NCT03494101
Recruitment Status : Unknown
Verified June 2018 by University of Zurich.
Recruitment status was:  Recruiting
First Posted : April 11, 2018
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
University of Zurich

Tracking Information
First Submitted Date March 1, 2018
First Posted Date April 11, 2018
Last Update Posted Date July 3, 2018
Actual Study Start Date June 15, 2018
Estimated Primary Completion Date January 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 3, 2018)
Genomic mutations in non-typhoid Salmonella strains [ Time Frame: 4 weeks after index stool culture ]
Analyze the evolution of non-typhoid Salmonella during acute infection and remission in humans. The primary variable of interest is the number of observed genomic mutations in non-typhoid Salmonella strains.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 3, 2018)
  • Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors [ Time Frame: 4 weeks after index stool culture ]
    Total number of Salmonella genes associated with tissue invasion Total number of antibiotic resistance genes Total number of virulence factor genes
  • Identification of most frequently mutated surface antigenes of non-typhoid Salmonella [ Time Frame: 4 weeks after index stool culture ]
    Identification of escape mechanisms of non-typhoid Salmonella (i.e. mutation of surface antigens) to avoid specific immune responses (i.e. antibodies) during acute infection and remission.
  • Gen Cluster Expression [ Time Frame: 2 weeks, 4 weeks and 6 months after index stool culture ]
    Identification of Salmonella gene clusters expressed during early phases of infection compared to remission.
  • Mutated non-typhoid Salmonella strains [ Time Frame: 4 weeks and 6 months after index stool culture ]
    Quantification of mutated non-typhoid Salmonella strains that escape specific immune responses.
  • Microbiota changes [ Time Frame: 2 weeks, 4 weeks and 6 months after index stool culture ]
    Composition (i.e. number of bacteria species identified) and relative diversity of the gut microbial community during acute non-typhoid Salmonella infection and remission. Findings will be compared to changes occurring in the microbiota of healthy individuals and individuals with acute, infectious diarrhea caused by microorganisms other than Salmonella.
  • Antibody producing cells [ Time Frame: 2 weeks and 4 weeks after index stool culture ]
    Composition (i.e. number of antibody-producing cells) and relative diversity of antibody-producing cells specific for non-typhoid Salmonella.
  • Antibody producing B-cell clones [ Time Frame: 4 weeks after index stool culture ]
    Number of antibody-producing cell clones (and their corresponding antibodies) against non-typhoid Salmonella isolated from peripheral blood B cells of subjects during remission. Measured variable: Number of Salmonella-specific B-cells per ml blood 4 weeks after infection.
  • Antibody repertoire [ Time Frame: 2 weeks and 4 weeks after index stool culture ]
    Identification of the antibody repertoire against non-typhoid Salmonella during acute infection in peripheral blood. Measured variable: Antibody titers against various non-typhoid Salmonella strains.
  • Antigen- Antibody recognition [ Time Frame: 4 weeks and 6 months after index stool culture ]
    Number of antigens of non-typhoid Salmonella recognized by the antibodies isolated from the previous endpoint.
  • Development of irritable bowel syndrome [ Time Frame: End of observational period (6 months) ]
    Number of patients who develop an irritable bowel syndrome after a non-typhoid Salmonella infection.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
Official Title Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
Brief Summary Stool and blood samples from patients with a non-typhoid Salmonella infection will be collected during an observation period of six months and analyzed for changes in the microbiota diversity and composition, mutation rates in the Salmonella strains and the specific immune response evoked by the infection. Findings are compared to healthy individuals and individuals with acute, infectious diarrhea caused by other microorganisms.
Detailed Description

Infection processes of a non-typhoid Salmonella infection in humans are not well understood and so far, only little research has been conducted in this area. Findings from preclinical studies, using mouse models, attributed a fundamental role in infection control to the gut microbiota and the host immune system (antibody response). In mouse models a non-typhoid Salmonella infection provokes a pronounced antibody response and salmonella-inflicted gut inflammation alters the microbiota diversity and composition in the gut lumen. To date there is only scarce evidence on similar effects in humans.

During the study, longitudinal stool and blood samples will be collected from patients with a non-typhoid Salmonella infection at different study time points (2 weeks, 4 weeks and 6 months after positive Salmonella stool culture) and analyzed for changes in the microbiota, mutation rates in the Salmonella strains and the specific immune response evoked by the infection (e.g. anti-bodies). At each study time point clinical information will be investigated with a questionnaire to assess current symptoms, medication etc. Findings will be compared to healthy individuals and patients with acute, infectious diarrhea caused by other microorganisms than non-typhoid Salmonella.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood and stool samples
Sampling Method Non-Probability Sample
Study Population 20 patients with a non-typhoid Salmonella infection, 10 patients with acute, infectious diarrhea without non-typhoid Salmonella infection, 10 healthy individuals
Condition Salmonella Infection Non-Typhoid
Intervention
  • Other: Blood samples
    Blood samples will be collected and analyzed at different study time points
  • Other: Stool samples
    Stool samples will be collected and analyzed at different study time points
  • Other: Clinical information
    Clinical information will be collected at different study time points using questionnaires
Study Groups/Cohorts
  • Non-typhoid Salmonella infection
    Patients with a non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected.
    Interventions:
    • Other: Blood samples
    • Other: Stool samples
    • Other: Clinical information
  • Acute, infectious diarrhea
    Patients with acute, infectious diarrhea without non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected.
    Interventions:
    • Other: Blood samples
    • Other: Stool samples
    • Other: Clinical information
  • Healthy individuals
    Healthy individuals with no symptoms of acute or chronic diarrhea. Blood samples, stool samples and clinical information will be collected.
    Interventions:
    • Other: Blood samples
    • Other: Stool samples
    • Other: Clinical information
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: April 3, 2018)
40
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 31, 2020
Estimated Primary Completion Date January 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

General inclusion criteria:

  • Signed informed consent.
  • Ability to understand and follow study procedures and understand informed consent
  • Age 18-75 years.

Inclusion criteria for patients with non-typhoid Salmonella infection (n=20)

  • Acute diarrhea (≥3 bowel movements per day for ≤4 weeks)
  • Stool cultures positive for non-typhoid Salmonella ≤4 weeks before inclusion

Inclusion criteria for patients with acute, infectious diarrhea without non-typhoid Salmonella infection (n=10)

  • Acute diarrhea (≥3 bowel movements per day for ≤4 weeks)
  • Stool cultures negative for non-typhoid Salmonella infection within ≤ 4 weeks

Inclusion criteria for healthy volunteers (n=10)

• No symptoms of acute or chronic diarrhea (2 bowel movements per week to 2 per day)

Exclusion Criteria:

  • Current use of antibiotics
  • Medication with immunosuppressants (e.g. corticoids, biological therapy).
  • Major medical/surgical/psychiatric condition requiring ongoing management. Minor well controlled conditions (i.e. medically controlled arterial hypertension, occupational asthma) may be present.
  • Major diagnosis known to chronically affect gut microbiota (e.g. inflammatory bowel disease, liver cirrhosis, colon carcinoma, systemic sclerosis).
  • Current diagnosis of a hematological disorder (e.g. severe anemia with hemoglobin <7 g/dl, leukemia) or any other absolute contraindication for blood donation.
  • Participation in other clinical study interfering with study procedures.
  • Inability to understand study procedures in order to provide inform consent.
  • Previous participation in the same study.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number NCT03494101
Other Study ID Numbers SALMONELLA Study
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party University of Zurich
Study Sponsor University of Zurich
Collaborators Not Provided
Investigators
Principal Investigator: Benjamin Misselwitz, PD Dr.med. Division of Gastroenterology, University Hospital Zurich Zurich, Switzerland, 8091
PRS Account University of Zurich
Verification Date June 2018