Safety and Viability of an E. Coli Nissle Colibactin Knockout in Healthy Volunteers (SECONI)

May 22, 2024 updated by: Max Nieuwdorp
E. coli Nissle (EcN) is a well-established human probiotic. However, it has been found that it produces colibactin, linked to colorectal cancer. In this safety trial, the safety and properties of a novel, colibactin-knockout EcN strain (EcNΔClbP) is investigated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In this randomised controlled intervention study, the investigators will compare EcN vs. EcN colibactin-knockout (EcNΔClbP), given once daily for 7 days, in a population of healthy individuals. Safety will be established using adverse event reporting, study visits and laboratory parameters. Pharmacokinetics will be established at the beginning and the end of the study. EcN/EcNΔClbP gut engraftment properties and effects on gut microbiome composition will be assessed using fecal analyses (qPCR, shotgun metagonmics). In addition, effects on glucose homeostasis will be studied using continuous glucose monitoring.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

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

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Amsterdam UMC Location AMC

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion criteria:

  • Healthy male or female of Caucasian descent

    • If female, postmenopausal
  • Age: 18-65 years old
  • BMI: 18-25 kg/m2
  • Subjects should be able to give informed consent

Exclusion Criteria:

  • Use of any systemic medication (except for paracetamol), including proton pump inhibitors, antibiotics and pro-/prebiotics in the past three months or during the study period.
  • Use of the EcN probiotic strain (Mutaflor®) in the past 12 months.
  • (Expected) prolonged comprised immunity (e.g. due to recent cytotoxic chemotherapy or human immunodeficiency viruses (HIV) infection with a CD4-T cell count < 240/mm3).
  • History of moderate to severe disease of the digestive tract, such as celiac disease, chronic diarrhoea (≥3 stools/day for >4 weeks), chronic obstipation (<2 defecations/week for >3 months), Irritable Bowel Syndrome (IBS) (according to Rome IV criteria) or Inflammatory Bowel Disease (IBD).
  • Any gastro-intestinal disorder within the past 6 months
  • Smoking or illicit drug use (e.g. amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period.
  • Use of >21 units of alcohol per week on average in the past three months or use of >2 units of alcohol during the study period.
  • Simultaneous participation in other studies

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: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: EcN
E Coli Nissle wildtype 10^11 once daily for 7 days
Dietary supplement: E Coli Nissle
E Coli wildtype strain
Experimental: EcN colibactin-knockout
EcN colibactin-knockout 10^11 once daily for 7 days
Dietary supplement: EcN Colibactin knockout
E coli Nissle strain with ClbP-gene removed and therefore not producing colibactin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: 3 weeks
The number, duration and severity of adverse reactions to assess the safety/tolerability of the EcNΔClbP strain compared to the wild type strain.
3 weeks
CRP
Time Frame: Weekly, during 3 weeks
Changes in CRP (mg/L)
Weekly, during 3 weeks
Leucocytes
Time Frame: Weekly, during 3 weeks
Changes in leucocytes (10^9/L)
Weekly, during 3 weeks
Renal function
Time Frame: Weekly, during 3 weeks
Changes in renal function, expressed as kreatinin levels (micromol/L) throughout the study
Weekly, during 3 weeks
Bilirubin
Time Frame: Weekly, during 3 weeks
Changes in bilirubin in micromol/L throughout the study
Weekly, during 3 weeks
alkaline phosphatase
Time Frame: Weekly, during 3 weeks
Changes in alkaline phosphatase in U/L throughout the study
Weekly, during 3 weeks
gamma-GT in U/L
Time Frame: Weekly, during 3 weeks
Changes in gamma-GT in U/L throughout the study
Weekly, during 3 weeks
AST
Time Frame: Weekly, during 3 weeks
Changes in AST in U/L throughout the study
Weekly, during 3 weeks
ALT
Time Frame: Weekly, during 3 weeks
Changes in ALT in U/L throughout the study
Weekly, during 3 weeks
Hemoglobin
Time Frame: Weekly, during 3 weeks
Changes in hemoglobin in mmol/L throughout the study
Weekly, during 3 weeks
trombocytes
Time Frame: Weekly, during 3 weeks
Changes in trombocytes in 10^9/L throughout the study
Weekly, during 3 weeks
eosinophils
Time Frame: Weekly, during 3 weeks
Changes in eosinophils in 10^9/L throughout the study
Weekly, during 3 weeks
basophils
Time Frame: Weekly, during 3 weeks
Changes in basophils in 10^9/L throughout the study
Weekly, during 3 weeks
neutrophils
Time Frame: Weekly, during 3 weeks
Changes in neutrophils in 10^9/L throughout the study
Weekly, during 3 weeks
monocytes
Time Frame: Weekly, during 3 weeks
Changes in monocytes in 10^9/L throughout the study
Weekly, during 3 weeks
Lipid profile
Time Frame: Weekly, during 3 weeks
Changes in lipid profile throughout the study
Weekly, during 3 weeks
Homeostatic model of insulin resistance (HOMA-IR)
Time Frame: Weekly, during 3 weeks
Changes in HOMA-IR throughout the study
Weekly, during 3 weeks
Gastro-intestinal quality of life - questionnaire
Time Frame: Weekly, during 3 weeks
Changes in Gastro-intestinal quality of life (GIQLI) score. The maximum score is 155, the minimum score is 31. A higher score represents a better outcome.
Weekly, during 3 weeks
Bristol Stool Chart
Time Frame: Weekly, during 3 weeks
Changes in Bristol Stool Chart score throughout the study. Stools can be scored from 1 (hard stool) to 7 (watery stool). A score of 4 is considered ideal.
Weekly, during 3 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of copies of EcN (qPCR)
Time Frame: Daily during 2 weeks
Quantification of EcN in faeces samples collected throughout the two weeks via quantitative polymerase chain reaction (qPCR)
Daily during 2 weeks
Microbiome composition
Time Frame: Weekly during 3 weeks
Comparison of relative abundances of species throughout the study using shotgun metagenomics
Weekly during 3 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Fecal 24h bile acids
Time Frame: Weekly during 3 weeks
Changes in 24h faecal bile acids will be measured at V2, V3 and V4.
Weekly during 3 weeks
Fasting blood bile acids
Time Frame: Weekly during 3 weeks
Changes in fasting plasma bile acids will be measured at V2, V3 and V4.
Weekly during 3 weeks
Fecal 24h short chain fatty acids
Time Frame: Weekly during 3 weeks
Changes in 24h faecal and fasting and short-chain fatty acids will be measured at V2, V3 and V4.
Weekly during 3 weeks
Fasting blood short chain fatty acids
Time Frame: Weekly during 3 weeks
Changes in fasting short-chain fatty acids will be measured at V2, V3 and V4.
Weekly during 3 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Max Nieuwdorp

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 18, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 19, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 19, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 9, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 18, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL83158.018.22

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

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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