To assses safety, gut engraftment and effects on sugar- and alcohol metabolism of d. piger in individuals with increased waist circumference.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The principal outcome will be patient safety and tolerability (biochemical
parameters of kidney and liver function and complete blood count, adverse
events as compared to placebo) and engraftment of D. piger in the gut as
compared to placebo.
Secondary outcome
Response to fructose challenge test during fomepizol infusion (including
fructose metabolites in blood, feces, urine and breath)
Transcriptomics in duodenal biopsies
Microbiome compostion (fecal shotgun metagenomics)
Fructose metabolites in 24 feces and 24h urine
Quality of Life questionnaires
Alcohol production per gram feces using bioreactor analyses
Glycemic control using continuous glucose monitoring
Liver fat, assessed using MRI liver and Fibroscan (V2 and V5)
Background summary
Fructose is a sugar that is much sweeter than glucose, and has multiple
applications in the food industry. Research shows that fructose is associated
with obesity, diabetes and cardiovascular disease. An overload of fructose may
be handled in the colon, where it is metabolized to alcohol by gut bacteria,
putatively contributing to fatty liver disease. Some bacteria degrade alcohol
in the colon, thereby protecting the body from deleterious effects. One of
these bacteria is d. piger. Our research group found that d. piger degrades
alcohol to acetate, that can be used by other bacteria to produce beneficial
metabolites. The current study aims to investigate whether d piger in humans is
safe and can lower the alcohol concentration in the blood after an oral
fructose challenge. In addition, the effects of d. piger on sugar- and fat
metabolism are established. If safe and effective, d piger can be a new therapy
or prevention measure for diseases such as fatty liver disease.
Study objective
To assses safety, gut engraftment and effects on sugar- and alcohol metabolism
of d. piger in individuals with increased waist circumference.
Study design
A phase I/II, placebo controlled, double blinded safety trial in 2x 10
participants.
Intervention
Participants will be given placebo or 10^9 colony forming units (CFU)/ml of
oral D. piger once daily for 4 weeks (n=10 per arm, total of 20 participants).
Study burden and risks
The overall risk of the study is estimated to be moderate, mainly due to the
risk of gastroduodenoscopy of bleeding or gastric perforation.
As D. piger is a gut commensal, few side effects are expected. In an earlier
trial on D. piger in a dose and duration exceeding ours, no side effects were
observed. Fomipezol can cause headache and somnolence in a minority of cases.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Increased waist circumference (>102 cm men, 88>cm women)
- Insulin resistance (HOMA-IR >2,5)
- 18-70 years
Exclusion criteria
- Use of systemic medication (except for paracetamol), including proton pump
inhibitors, 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
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85441.018.23 |