diabetes Diabetes mellitus
Conditions
Interventions
The investigational products are the EcN&Delta
ClbP strain and the active comparator
is the wildtype EcN strain. The wildtype EcN strain is a well-established, safe
human probiotic and has been used for over a century [3]. Participants will be
ClbP strain daily for 7
days. In the control group, subjects will receive 1011 CFU of the wildtype EcN
strain daily for 7 days. Both strains will be produced under HACCP guidelines
by NIZO, Ede, th
Sponsors
Amsterdam UMC
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Healthy male or female of Caucasian descent o If female, postmenopausal - Age: 18-65 years old - BMI: 18-25 kg/m2 - Subjects should be able to give informed consent
Exclusion criteria
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 count =3 stools/day for >4 weeks), chronic obstipation (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. MDMA/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. - Pregnancy or breast feeding - Simultaneous participation in other studies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome is the number, duration and severity of adverse reactions to assess the safety/tolerability of the EcNΔClbP strain compared to the wild type strain. In addition, changes in inflammatory markers (CRP, leukocytes) will be measured as well as blood safety parameters (liver and renal function, complete blood count, lipids and glucose/insulin) at V2, V3 and V4. Finally, quality of life, gastrointestinal (GI) comfort and stool metrics are recorded through validated questionnaires (gastro-intestinal quality of life, GIQLI, and Bristol Stool Chart) at V2, V3 and V4. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcomes include: - Quantific ation of EcN in faeces samples collected throughout the two weeks via qPCR to assess engraftment, viability and washout of the EcN. - (Anaerobic) culturing of fresh faeces samples (V2, V3 and V4) on EcN selective media to assess engraftment, viability and washout of the EcN. - Staining of EcN ribosomal RNA to assess engraftment, viability and washout of the EcN. - Metagenomic sequencing will be performed on faecal samples from V2, V3 and V4 to study the effect of the intervention on the gut microbiota composition and to mathematically assess the growth/engraftment of the EcN in situ (peak-to-trough ratio). In addition, the effect of gut microbiota composition on engraftment of both EcN strains will be assessed. Other study parameters include: - Changes in glucose metabolism, measured by CGM (freestyle libre) during the week before intervention and two weeks thereafter. - Changes in 24h faecal and fasting plasma bile acids and SCFA will be measured at V2, V3 and V4. - Bristol Stool Chart score at V2, V3 and V4 - Physical parameters (length, weight, blood pressure, body impedance analysis) at V2, V3 and V4 - Dietary intake during the week prior to the intervention and the two-week study period. | — |
Countries
Netherlands
Outcome results
None listed