DiabetesPhase 1SECONINCT05816577
Safety and Viability of an E. Coli Nissle Colibactin Knockout in Healthy Volunteers
A Phase 1 study testing EcN Colibactin knockout and E Coli Nissle in people with Diabetes, run by Max Nieuwdorp at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes
- What is being tested?
- EcN Colibactin knockout and E Coli Nissle
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 18 Sep 2023to 19 Mar 2024
- Phase
- Phase 1
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
- 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.
Read the 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.
- Conditions
- Diabetes
- Being tested
- EcN Colibactin knockout, E Coli Nissle
- Keywords
- advanced microbiome therapeutics, diabetes, safety
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EcN Colibactin knockoutDietary supplement
E coli Nissle strain with ClbP-gene removed and therefore not producing colibactin
E Coli NissleDietary supplement
E Coli wildtype strain
| Study group | Role | What they receive |
|---|---|---|
| EcN | Active comparator | E Coli Nissle wildtype 10^11 once daily for 7 days Receives: Dietary Supplement: E Coli Nissle |
| EcN colibactin-knockout | Experimental | EcN colibactin-knockout 10^11 once daily for 7 days Receives: Dietary Supplement: EcN Colibactin knockout |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
The number, duration and severity of adverse reactions to assess the safety/tolerability of the EcNΔClbP strain compared to the wild type strain.
Measured: 3 weeks
CRP
Changes in CRP (mg/L)
Measured: Weekly, during 3 weeks
Leucocytes
Changes in leucocytes (10^9/L)
Measured: Weekly, during 3 weeks
Renal function
Changes in renal function, expressed as kreatinin levels (micromol/L) throughout the study
Measured: Weekly, during 3 weeks
Bilirubin
Changes in bilirubin in micromol/L throughout the study
Measured: Weekly, during 3 weeks
alkaline phosphatase
Changes in alkaline phosphatase in U/L throughout the study
Measured: Weekly, during 3 weeks
gamma-GT in U/L
Changes in gamma-GT in U/L throughout the study
Measured: Weekly, during 3 weeks
AST
Changes in AST in U/L throughout the study
Measured: Weekly, during 3 weeks
ALT
Changes in ALT in U/L throughout the study
Measured: Weekly, during 3 weeks
Hemoglobin
Changes in hemoglobin in mmol/L throughout the study
Measured: Weekly, during 3 weeks
trombocytes
Changes in trombocytes in 10^9/L throughout the study
Measured: Weekly, during 3 weeks
eosinophils
Changes in eosinophils in 10^9/L throughout the study
Measured: Weekly, during 3 weeks
basophils
Changes in basophils in 10^9/L throughout the study
Measured: Weekly, during 3 weeks
neutrophils
Changes in neutrophils in 10^9/L throughout the study
Measured: Weekly, during 3 weeks
monocytes
Changes in monocytes in 10^9/L throughout the study
Measured: Weekly, during 3 weeks
Lipid profile
Changes in lipid profile throughout the study
Measured: Weekly, during 3 weeks
Homeostatic model of insulin resistance (HOMA-IR)
Changes in HOMA-IR throughout the study
Measured: Weekly, during 3 weeks
Gastro-intestinal quality of life - questionnaire
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.
Measured: Weekly, during 3 weeks
Bristol Stool Chart
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.
Measured: Weekly, during 3 weeks
Secondary outcomes (2)
Number of copies of EcN (qPCR)
Quantification of EcN in faeces samples collected throughout the two weeks via quantitative polymerase chain reaction (qPCR)
Measured: Daily during 2 weeks
Microbiome composition
Comparison of relative abundances of species throughout the study using shotgun metagenomics
Measured: Weekly during 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2023
- Study start18 Sep 2023
- Primary completion19 Mar 2024
- Study completion19 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomised, controlled, safety study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Max Nieuwdorp
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Max Nieuwdorp, Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05816577
- Sponsor's protocol ID
- NL83158.018.22
- Acronym
- SECONI
- Status last verified
- May 2024
- First submitted
- 9 Mar 2023
- Last updated
- 23 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Viability of an E. Coli Nissle Colibactin Knockout in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05816577
- Acronym / sponsor ID
- SECONI / NL83158.018.22
- Conditions
- Diabetes
- Keywords
- advanced microbiome therapeutics, diabetes, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Max NieuwdorpUniversity, hospital or other
- Study start
- 18 Sep 2023 (actual)
- Primary completion
- 19 Mar 2024 (actual)
- Study completion
- 19 Mar 2024 (actual)
- First posted
- 18 Apr 2023 (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.
- 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Double-blind, randomised, controlled, safety study
| Arm | Type | Receives |
|---|---|---|
| EcN | Active comparator | Dietary Supplement: E Coli NissleE Coli Nissle wildtype 10^11 once daily for 7 days |
| EcN colibactin-knockout | Experimental | Dietary Supplement: EcN Colibactin knockoutEcN colibactin-knockout 10^11 once daily for 7 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Healthy male or female of Caucasian descent
- Age: 18-65 years old
- BMI: 18-25 kg/m2
- Subjects should be able to give informed consent
Key exclusion criteria (8 listed)
- 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
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 |
|---|---|---|
| EcN Colibactin knockoutE coli Nissle strain with ClbP-gene removed and therefore not producing colibactin | Dietary supplement | EcN colibactin-knockout |
| E Coli NissleE Coli wildtype strain | Dietary supplement | EcN |
Primary outcome
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.
CRP
Time frame: Weekly, during 3 weeks
Changes in CRP (mg/L)
Leucocytes
Time frame: Weekly, during 3 weeks
Changes in leucocytes (10^9/L)
Renal function
Time frame: Weekly, during 3 weeks
Changes in renal function, expressed as kreatinin levels (micromol/L) throughout the study
Bilirubin
Time frame: Weekly, during 3 weeks
Changes in bilirubin in micromol/L throughout the study
alkaline phosphatase
Time frame: Weekly, during 3 weeks
Changes in alkaline phosphatase in U/L throughout the study
gamma-GT in U/L
Time frame: Weekly, during 3 weeks
Changes in gamma-GT in U/L throughout the study
AST
Time frame: Weekly, during 3 weeks
Changes in AST in U/L throughout the study
ALT
Time frame: Weekly, during 3 weeks
Changes in ALT in U/L throughout the study
Hemoglobin
Time frame: Weekly, during 3 weeks
Changes in hemoglobin in mmol/L throughout the study
trombocytes
Time frame: Weekly, during 3 weeks
Changes in trombocytes in 10^9/L throughout the study
eosinophils
Time frame: Weekly, during 3 weeks
Changes in eosinophils in 10^9/L throughout the study
basophils
Time frame: Weekly, during 3 weeks
Changes in basophils in 10^9/L throughout the study
neutrophils
Time frame: Weekly, during 3 weeks
Changes in neutrophils in 10^9/L throughout the study
monocytes
Time frame: Weekly, during 3 weeks
Changes in monocytes in 10^9/L throughout the study
Lipid profile
Time frame: Weekly, during 3 weeks
Changes in lipid profile throughout the study
Homeostatic model of insulin resistance (HOMA-IR)
Time frame: Weekly, during 3 weeks
Changes in HOMA-IR throughout the study
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.
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.
2 secondary outcomes
Number of copies of EcN (qPCR)
Time frame: Daily during 2 weeks
Microbiome composition
Time frame: Weekly during 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2024.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EcN Colibactin knockout and E Coli Nissle in people with Diabetes, run by Max Nieuwdorp at 1 site in Netherlands.
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 5 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: finished, as of the sponsor's last update on 23 May 2024. 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 Netherlands. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: 3 weeks). The study lists 19 primary outcomes in all. 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 23 May 2024; AzTrials last refreshed its copy on 7 Nov 2026.