Clinical trial NCT05816577: Safety and Viability of an E. Coli Nissle Colibactin Knockout in Healthy Volunteers
Official title: Safety and Viability of an E. Coli Nissle Colibactin Knockout in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Keywords: advanced microbiome therapeutics
diabetes
safety
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2023-04-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomised, controlled, safety study
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events
timeFrame: 3 weeks
measure: CRP
timeFrame: Weekly, during 3 weeks
measure: Leucocytes
timeFrame: Weekly, during 3 weeks
measure: Renal function
timeFrame: Weekly, during 3 weeks
measure: Bilirubin
timeFrame: Weekly, during 3 weeks
measure: alkaline phosphatase
timeFrame: Weekly, during 3 weeks
measure: gamma-GT in U/L
timeFrame: Weekly, during 3 weeks
measure: AST
timeFrame: Weekly, during 3 weeks
measure: ALT
timeFrame: Weekly, during 3 weeks
measure: Hemoglobin
timeFrame: Weekly, during 3 weeks
measure: trombocytes
timeFrame: Weekly, during 3 weeks
measure: eosinophils
timeFrame: Weekly, during 3 weeks
measure: basophils
timeFrame: Weekly, during 3 weeks
measure: neutrophils
timeFrame: Weekly, during 3 weeks
measure: monocytes
timeFrame: Weekly, during 3 weeks
measure: Lipid profile
timeFrame: Weekly, during 3 weeks
measure: Homeostatic model of insulin resistance (HOMA-IR)
timeFrame: Weekly, during 3 weeks
measure: Gastro-intestinal quality of life - questionnaire
timeFrame: Weekly, during 3 weeks
measure: Bristol Stool Chart
timeFrame: Weekly, during 3 weeks
Secondary outcomes:
measure: Number of copies of EcN (qPCR)
timeFrame: Daily during 2 weeks
measure: Microbiome composition
timeFrame: Weekly during 3 weeks
Other outcomes:
measure: Fecal 24h bile acids
timeFrame: Weekly during 3 weeks
measure: Fasting blood bile acids
timeFrame: Weekly during 3 weeks
measure: Fecal 24h short chain fatty acids
timeFrame: Weekly during 3 weeks
measure: Fasting blood short chain fatty acids
timeFrame: Weekly during 3 weeks
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC location AMC
Study officials:
References: