To investigate whether single dosis of fecal therapy by infusion of allogeneic (post bariatric surgery donor feces in the bowel) or autologous (own feces) have differential effect on lipid-metabolism-mediated insulin resistance.
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Glucose metabolism disorders (incl diabetes mellitus)
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Changes in insulin sensitivity and de novo lipogenesis as measured by
hyperinsulinemic euglycemic clamp with stable isotopes at 0 and 2 weeks and by
measuring energy excretion, short chain fatty acids profile and bile acid
concentration in 2x 24h collected feces.
Secondary outcome
Secondary and further study parameters needed to answer the research question:
Changes in adipose tissue inflammation by subcutaneous adipose tissue biopsy
(to assess phosphorylation status of the insulin signalling cascade in relation
to metabolic genes (perilipin3) and to evaluate dipose tissue inflammation
(macrophage counts). Inflammatory markers in serum will also be measured.
Tertiary end points:
small and large intestinal microbiota in relation to intestinal transit time
(segmental SITZMARKS) at 0 and 2 weeks.
Background summary
Recent research suggests that obesity is associated with variations in bowel
flora composition (Vrieze, FATLOSE-1-trial, Gastroenterology 2012)
Interestingly, this seemingly bacteria-associated condition is transmissible:
colonization of obese mice with a *lean microbiota* results in a significantly
greater decrease in total body fat (-30%) than colonization with an *obese
microbiota* (+5%). Moreover fecal transplants from lean human donors were found
to improve peripheral and hepatic insulin resistance and glucose and lipid
metabolism in male patients with metabolic syndrome [Vrieze et al. GE FATLOSE
1].
Bariatric surgery is an increasingly employed intervention in morbidly obese
patients. Bariatric surgery (gastric bypass or GBP) has not only a weight
dependent, but also a weight-independent mitigating effect on insulin
resistance [Laferrère et al 2012]. A significant increase in incretin level and
effect is seen after GBP that is not seen after weight loss due to calory
restriction alone [Laferrère, JCEM, 2008]. This led to the hypothesis that
bowel factors including bowel transit time are involved rather than abdominal
fat cell factors. The intestinal microbiota might play a significant role.
Recent investigation indicates that T2D-mice have reduced insulin resistance
after transplantation with microbiota from patients that have undergone GBP
[Liou, Science Translational Medicine 2013].. It is our aim to investigate this
principle in humans.
Our hypothesis is that intestinal microbes have a differential effect on
bacterial translocation, intestinal transit time and lipid metabolism. These
are interrelated and each contribute to systemic inflammatory processes (such
as adipose tissue inflammation) that lead to insulin resistance.
Study objective
To investigate whether single dosis of fecal therapy by infusion of allogeneic
(post bariatric surgery donor feces in the bowel) or autologous (own feces)
have differential effect on lipid-metabolism-mediated insulin resistance.
Study design
Single blind randomized controlled single center trial.
Intervention
Patients will be randomised to one of the two treatment arms: single allogeneic
feces (post bariatric surgery donor feces in the bowel by duodenal tube) vs.
single allogeneic feces from a pre-bariatric surgery donor.
Study burden and risks
2 gastroscopies, 2 insuline-glucose-clamps with resting energy expenditure
measurement and glycerol isotope bolus infusion, 2 adipose tissue biopsies, 5
abdominal X-rays. Minimal health risks (<0.01% perforation with gastroscopy)
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Patients:
Males
Meeting the criteria for metabolic syndrome (ATP-III criteria)
No relevant (confounding) comorbidity or medication use;Feces donors post-RYGB:
Males
+- 1 year after gastric bypass with significant weight loss
No relevant (confounding) comorbidity
free of transmissible diseases upon screening;Feces donors pre-RYGB:
Males
Scheduled for gastric bypass (RYGB)
No relevant (confounding) comorbidity
free of transmissible diseases upon screening
Exclusion criteria
Patients:
relevant comorbidity
additional medication use except when directly related to metabolic syndrome
antibiotic use in the last 3 months;Feces donors (pre- and post-RYGB):
relevant morbidity
medication use
PPI or antibiotic use in the last 3 months
frequent patient contact
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 | NL43964.018.13 |