Salmonella Infection Non-TyphoidNCT03494101
Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
An observational study of Salmonella Infection Non-Typhoid, run by University of Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Salmonella Infection Non-Typhoid
- What is being tested?
- Blood samples, Stool samples and Clinical information
- How many people
- 40 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 Jun 2018to 31 Jan 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 20 patients with a non-typhoid Salmonella infection, 10 patients with acute, infectious diarrhea without non-typhoid Salmonella infection, 10 healthy individuals
Who may be able to join
- 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)
Show all 11Show fewer
- 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
- No symptoms of acute or chronic diarrhea (2 bowel movements per week to 2 per day)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Division of Gastroenterology, University Hospital Zurich
Zurich, 8091
Gerhard Rogler, MD PhD, ++41 44 255 9519, gerhard.rogler@usz.ch
Benjamin Misselwitz, MD, ++41 44 255 1111, benjamin.misselwitz@usz.ch
About this study
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.
Read the 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.
- Conditions
- Salmonella Infection Non-Typhoid
- Being tested
- Blood samples, Stool samples, Clinical information
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplesOther
Blood samples will be collected and analyzed at different study time points
Stool samplesOther
Stool samples will be collected and analyzed at different study time points
Clinical informationOther
Clinical information will be collected at different study time points using questionnaires
| Study group | Role | What they receive |
|---|---|---|
| Non-typhoid Salmonella infection | Patients with a non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected. Receives: 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. Receives: 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. Receives: Other: Blood samples; Other: Stool samples; Other: Clinical information |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genomic mutations in non-typhoid Salmonella strains
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.
Measured: 4 weeks after index stool culture
Secondary outcomes (10)
Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors
Total number of Salmonella genes associated with tissue invasion Total number of antibiotic resistance genes Total number of virulence factor genes
Measured: 4 weeks after index stool culture
Identification of most frequently mutated surface antigenes of non-typhoid Salmonella
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.
Measured: 4 weeks after index stool culture
Gen Cluster Expression
Identification of Salmonella gene clusters expressed during early phases of infection compared to remission.
Measured: 2 weeks, 4 weeks and 6 months after index stool culture
Mutated non-typhoid Salmonella strains
Quantification of mutated non-typhoid Salmonella strains that escape specific immune responses.
Measured: 4 weeks and 6 months after index stool culture
Microbiota changes
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.
Measured: 2 weeks, 4 weeks and 6 months after index stool culture
Antibody producing cells
Composition (i.e. number of antibody-producing cells) and relative diversity of antibody-producing cells specific for non-typhoid Salmonella.
Measured: 2 weeks and 4 weeks after index stool culture
Antibody producing B-cell clones
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.
Measured: 4 weeks after index stool culture
Antibody repertoire
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.
Measured: 2 weeks and 4 weeks after index stool culture
Antigen- Antibody recognition
Number of antigens of non-typhoid Salmonella recognized by the antibodies isolated from the previous endpoint.
Measured: 4 weeks and 6 months after index stool culture
Development of irritable bowel syndrome
Number of patients who develop an irritable bowel syndrome after a non-typhoid Salmonella infection.
Measured: End of observational period (6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2018
- Study start15 Jun 2018
- Primary completion31 Jan 2020 (estimated)
- Study completion31 Jan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Salmonella Infection Non-TyphoidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin Misselwitz, PD Dr.med., Principal investigator, Division of Gastroenterology, University Hospital Zurich Zurich, Switzerland, 8091
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03494101
- Sponsor's protocol ID
- SALMONELLA Study
- Status last verified
- Jun 2018
- First submitted
- 1 Mar 2018
- Last updated
- 3 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
- ClinicalTrials.gov ID
- NCT03494101
- Acronym / sponsor ID
- SALMONELLA Study
- Conditions
- Salmonella Infection Non-Typhoid
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 15 Jun 2018 (actual)
- Primary completion
- 31 Jan 2020 (estimated)
- Study completion
- 31 Jan 2020 (estimated)
- First posted
- 11 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Non-typhoid Salmonella infection | – | Other: Blood samples, Other: Stool samples, Other: Clinical informationPatients with a non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected. |
| Acute, infectious diarrhea | – | Other: Blood samples, Other: Stool samples, Other: Clinical informationPatients with acute, infectious diarrhea without non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected. |
| Healthy individuals | – | Other: Blood samples, Other: Stool samples, Other: Clinical informationHealthy individuals with no symptoms of acute or chronic diarrhea. Blood samples, stool samples and clinical information will be collected. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 20 patients with a non-typhoid Salmonella infection, 10 patients with acute, infectious diarrhea without non-typhoid Salmonella infection, 10 healthy individuals
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samplesBlood samples will be collected and analyzed at different study time points | Other | Acute, infectious diarrhea, Healthy individuals, Non-typhoid Salmonella infection |
| Stool samplesStool samples will be collected and analyzed at different study time points | Other | Acute, infectious diarrhea, Healthy individuals, Non-typhoid Salmonella infection |
| Clinical informationClinical information will be collected at different study time points using questionnaires | Other | Acute, infectious diarrhea, Healthy individuals, Non-typhoid Salmonella infection |
Primary outcome
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.
10 secondary outcomes
Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors
Time frame: 4 weeks after index stool culture
Identification of most frequently mutated surface antigenes of non-typhoid Salmonella
Time frame: 4 weeks after index stool culture
Gen Cluster Expression
Time frame: 2 weeks, 4 weeks and 6 months after index stool culture
Mutated non-typhoid Salmonella strains
Time frame: 4 weeks and 6 months after index stool culture
Microbiota changes
Time frame: 2 weeks, 4 weeks and 6 months after index stool culture
Antibody producing cells
Time frame: 2 weeks and 4 weeks after index stool culture
Antibody producing B-cell clones
Time frame: 4 weeks after index stool culture
Antibody repertoire
Time frame: 2 weeks and 4 weeks after index stool culture
Antigen- Antibody recognition
Time frame: 4 weeks and 6 months after index stool culture
Development of irritable bowel syndrome
Time frame: End of observational period (6 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2018.
Related trials for Salmonella Infection Non-Typhoid
Active, not recruiting
Challenge Non-Typhoidal Salmonella (CHANTS) Study
Salmonella Infections, Salmonella Typhimurium
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Misselwitz, PD Dr.med. principal investigator
Division of Gastroenterology, University Hospital Zurich Zurich, Switzerland, 8091
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Salmonella Infection Non-Typhoid, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Benjamin Misselwitz, PD Dr.med. (+41 44 255 1111, benjamin.misselwitz@usz.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genomic mutations in non-typhoid Salmonella strains (time frame: 4 weeks after index stool culture). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2018.