Metabolic Syndrome, Obesity, Steatosis of Liver
Conditions
Brief summary
The goal of the study is to determine the effect of supplementation of the d piger strain on intestinal ethanol production in individuals with overweight. The investigators will perform a randomized trial in 2x10 participants to measure effects on ethanol in blood, and perform fecal analyses.
Detailed description
The investigators perform a randomized, placebo controlled trial in 2x10 participants. The participants will be given placebo or d piger as an oral suspension once daily for 30 days. At baseline and after 30 days, a fructose challenge test with fomepizole, gastroduodenoscopy and MRI liver + FibroScan will be performed. Patient will attend the clinical trial unit weekly for safety visits. The participants will be overweight males or females age 18-70 with impaired glucose tolerance.
Interventions
DIETARY_SUPPLEMENTD piger
Probiotic d piger
DIETARY_SUPPLEMENTPlacebo
Placebo
Sponsors
Max Nieuwdorp
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The pharmacist will provide the study intervention to the investigator in a coded fashion. Both the investigator and the participant are blinded. In case of emergency, an unblinding protocol is activated.
Intervention model description
2x10 participants will be randomly allocated to placebo or d piger suspension once daily.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: Male or (postmenopausal) females * Increased waist circumference (\>102 cm men, 88\>cm women) * Insulin resistance (HOMA\>2.5) * 18-70 years
Exclusion criteria
* Use of systemic medication (except for paracetamol), including antibiotics and pro-/prebiotics in the past three months or during the study period. * A history of a cardiovascular event * A history of cholecystectomy * Overt untreated gastrointestinal disease or abnormal bowel habits * Liver enzymes\>2.5 fold higher than the upper limit of normal range * Smoking * Alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal function | 30 days | Number of participants with a decreased kidney function, defined as a rise in serum creatinine of \>26,5 micromol/L in 48 h |
| Gut engraftment | 30 days | the number of reads of d piger in feces using q pcr |
| adverse events | 30 days | the number of adverse events in both groups |
| Occurence of anemia | 30 days | Number of patients with Hb \< 8,5 mmol/L |
| Changes in leucocytes | 30 days | Number of patients with leucocytes \<4,0 or \>10,5 x10E9 cells/L |
| Changes in thrombocytes | 30 days | Number of patients with thrombocytes \<150 x 10E9 cells/ |
| Changes in aspartate aminotransferase (AST) | 30 days | Number of patients with AST \> 43 IU/L |
| Changes in alanine aminotransferase (ALT) | 30 days | Number of patients with ALT \> 45 IU/L |
| Changes in alkaline phosphatase (ALP) | 30 days | Number of patients with ALP \> 126 IU/L |
| Changes in Gamma-glutamyltransferase (GGT) | 30 days | Number of patients with GGT \> 117 IU/L |
| Changes in total bilirubin | 30 days | Number of patients with total bilirubin \> 24 micromol/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRI | 30 days | Liver fat measured by proton density fat fraction (PDFF) MRI liver |
| Fructose in peripheral blood | 30 days | Area under the curve of fructose in peripheral blood upon ingestion of 1 gram / kg unlabeled fructose in combination with 1000mg of D-fructose-13C6 |
| FibroScan | 30 days | Liver stiffness measured by FibroScan |
| Fructose metabolites in breath | 30 days | Area under the curve of various metabolites (e.g. ethanol) will be measured in breath samples upon ingestion of 1 gram / kg unlabeled fructose in combination with 1000mg of D-fructose-13C6 |
| Time-in-range | 30 days | Increase in Time-in-range (TIR,%), a parameter of continuous glucose monitoring devices, where TIR can be between 0 and 100%. A higher TIR reflects a better outcome. |
| Continuous glucose monitoring | 30 days | Decrease in glucose variability (GV, %), a parameter of continuous glucose monitoring devices, where GV can be between 0 and 100%. A lower GV reflects a better outcome. |
| Glycemic control | 30 days | Changes in fasting glucose (mmol/L) |
| Dietary intake | 30 days | Participants are asked to fill out an online dietary questionnaire for the 3 days prior to study visit 2,3,4,5 and 7 |
| Questionnaires | 30 days | Changes in Gastro-intestinal Quality of Life Index (GIQLI score) (points). The minimum and maximum score are 31 and 155 points respectively, and a higher score reflects a better outcome. |
| Intestinal microbiota composition | 30 days | Changes from baseline of relative abundance (%) of bacterial phyla, genera and species between groups and within participants. |
| Fructose metabolites in feces | 30 days | Using 24h feces, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as short chain fatty acids (SCFAs) and bile acids. |
| Fructose metabolites in urine | 30 days | Using 24h urine, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as SCFAs and bile acids. |
| Bioreactor analyses | 30 days | Using specific anaerobic culturing, ethanol production of fecal samples will be assessed of bacterial strains. |
Countries
Netherlands
Contacts
Primary ContactM Nieuwdorp, prof dr
Outcome results
None listed