- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03494101
Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Benjamin Misselwitz, PD Dr.med.
- Phone Number: +41 44 255 1111
- Email: benjamin.misselwitz@usz.ch
Study Locations
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-
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Zurich, Switzerland, 8091
- Recruiting
- Division of Gastroenterology, University Hospital Zurich
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Non-typhoid Salmonella infection
Patients with a non-typhoid Salmonella infection.
Blood samples, stool samples and clinical information will be collected.
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Blood samples will be collected and analyzed at different study time points
Stool samples will be collected and analyzed at different study time points
Clinical information will be collected at different study time points using questionnaires
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Acute, infectious diarrhea
Patients with acute, infectious diarrhea without non-typhoid Salmonella infection.
Blood samples, stool samples and clinical information will be collected.
|
Blood samples will be collected and analyzed at different study time points
Stool samples will be collected and analyzed at different study time points
Clinical information will be collected at different study time points using questionnaires
|
Healthy individuals
Healthy individuals with no symptoms of acute or chronic diarrhea.
Blood samples, stool samples and clinical information will be collected.
|
Blood samples will be collected and analyzed at different study time points
Stool samples will be collected and analyzed at different study time points
Clinical information will be collected at different study time points using questionnaires
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Genomic mutations in non-typhoid Salmonella strains
Time Frame: 4 weeks after index stool culture
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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.
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4 weeks after index stool culture
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors
Time Frame: 4 weeks after index stool culture
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Total number of Salmonella genes associated with tissue invasion Total number of antibiotic resistance genes Total number of virulence factor genes
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4 weeks after index stool culture
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Identification of most frequently mutated surface antigenes of non-typhoid Salmonella
Time Frame: 4 weeks after index stool culture
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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.
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4 weeks after index stool culture
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Gen Cluster Expression
Time Frame: 2 weeks, 4 weeks and 6 months after index stool culture
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Identification of Salmonella gene clusters expressed during early phases of infection compared to remission.
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2 weeks, 4 weeks and 6 months after index stool culture
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Mutated non-typhoid Salmonella strains
Time Frame: 4 weeks and 6 months after index stool culture
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Quantification of mutated non-typhoid Salmonella strains that escape specific immune responses.
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4 weeks and 6 months after index stool culture
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Microbiota changes
Time Frame: 2 weeks, 4 weeks and 6 months after index stool culture
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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.
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2 weeks, 4 weeks and 6 months after index stool culture
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Antibody producing cells
Time Frame: 2 weeks and 4 weeks after index stool culture
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Composition (i.e.
number of antibody-producing cells) and relative diversity of antibody-producing cells specific for non-typhoid Salmonella.
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2 weeks and 4 weeks after index stool culture
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Antibody producing B-cell clones
Time Frame: 4 weeks after index stool culture
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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.
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4 weeks after index stool culture
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Antibody repertoire
Time Frame: 2 weeks and 4 weeks after index stool culture
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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.
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2 weeks and 4 weeks after index stool culture
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Antigen- Antibody recognition
Time Frame: 4 weeks and 6 months after index stool culture
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Number of antigens of non-typhoid Salmonella recognized by the antibodies isolated from the previous endpoint.
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4 weeks and 6 months after index stool culture
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Development of irritable bowel syndrome
Time Frame: End of observational period (6 months)
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Number of patients who develop an irritable bowel syndrome after a non-typhoid Salmonella infection.
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End of observational period (6 months)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Benjamin Misselwitz, PD Dr.med., Division of Gastroenterology, University Hospital Zurich Zurich, Switzerland, 8091
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SALMONELLA Study
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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 register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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