|- candidate number||8555|
|- NTR Number||NTR2566|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||15-okt-2010|
|- Secondary IDs||10/265 MEC AMC|
|- Public Title||Effect antibiotics on gutmicrobiota composition & insulin resistance.|
|- Scientific Title||Effect of antibiotics on gut microbiota composition & insulin resistance in obese humans: Amoxycillin-vs-vancomycin trial.|
|- ACRONYM||A-V trial|
|- hypothesis||Accumulating data from both patients and animal models indicates that imbalances in the composition of the gut microbiota are related to obesity and its associated diseases However, the exact role of the microbiota and the mechanism mediating its impact on metabolic functions are poorly understood.|
Interestingly, antibiotics have been shown to produce drastic short- and long-term alterations of the human indwelling microbiota. After a 2 wk intervention with norfloxacin in combination with ampicillin the numbers of aerobic and anaerobic gut bacteria in ob/ob mice were maximally suppressed. The ob/ob mice showed a significant improvement in fasting glycemia and oral glucose tolerance by 30%. Concomitant reduction of liver triglycerides, reduction of lipopolysaccharides supported the antidiabetic effects of antibiotic treatment. This study showed that modulation of gut microbiota with antibiotics improved glucose tolerance in mice by altering the expression of hepatic and intestinal genes involved in inflammation and metabolism.
The mechanism by with gutmicrobiota affect glucose metabolism remains elusive, however some studies have suggested that bileacids are involved in human glucose and lipid metabolism We postulate that insulin resistance can be reduced reducing the numbers of specific gut microbiota by certain antibiotics. To test this hypothesis, we would like to investigate the effect of antibiotic treatment on gut microbiota composition, insulin resistance and bile acid metabolism in obese subjects.
|- Healt Condition(s) or Problem(s) studied||Obesity, Insulin resistance|
|- Inclusion criteria||1. Male obese subjects with metabolic syndrome (BMI > 30kg/m2, FPG>5.6 mmol/l);|
2. Age 20-65 yr;
3. No medication use.
|- Exclusion criteria||1. Patients with renal failure (kreatinine>135mmol/l);|
2. Liver function problems (ASAT/ALAT>2x upper limit);
3. Hypersensitivity to penicillin, amoxicillin, other beta lactams or chinolones;
4. Patients with medication known to interfere with glucose metabolism or bile acid composition (sequestrants, chenodiole, ursochol);
5. Patients with infectious mononucleosis;
6. Asthmatic patients;
7. Antibiotic use last three months;
8. Disorders known to interfere with bile acid metabolism (intestine resection, liver/intestine disorders);
9. History of laparoscopic cholecystectomy;
10. Patients with idiopathic diarrhea.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2011|
|- planned closingdate||1-mei-2011|
|- Target number of participants||20|
|- Interventions||Patients will be randomised to either 7 days amoxicillin 500mg 3dd or 7 days vancomycin 500mg 3dd. |
|- Primary outcome||The primary endpoint is changes in faecal flora composition after 7 days as well as 2, 4 and 6 weeks after the antibiotics. |
|- Secondary outcome||1. Changes in insulin resistance (assessed by hyperinsulinemic normoglycemic clamp at baseline and after 7 days);|
2. Bile acid and lipidmetabolism (assessed by MMT at baseline and after 7 days);
3. Changes in systemic inflammatory markers and lipid profiles at baseline as well as 7 days, 2, 4 and 6 weeks after antibiotics.
|- Timepoints||Baseline and 1,2,4 & 6 weeks after antibiotics.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Drs. A. Vrieze|
|- CONTACT for SCIENTIFIC QUERIES||Drs. A. Vrieze|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam|
(Source(s) of Monetary or Material Support)
|Academic Medical Center (AMC), Amsterdam|
|- Brief summary||Objective: |
To investigate the effect of antibiotic intervention on gut microbiota composition, insulin resistance and bile acid composition.
Two-arm, randomised, controlled single centre trial.
Male obese subjects with metabolic syndrome (BMI > 30kg/m2, FPG>5.6 mmol/l), age 20-65 yr, no medication use.
Patients will be randomised to either 7 days amoxicillin 500mg 3dd or 7 days vancomycin 250 mg 3dd 2.
The primary endpoint is changes in faecal flora composition after 7 days as well as 2, 4 and 6 weeks after the antibiotics. Secondary endpoints are changes in insulin resistance (assessed by hyperinsulinemic normoglycemic clamp at baseline and after 7 days), bile acid and lipidmetabolism (assessed by mixed meal test at baseline and after 7 days), as well as changes in systemic inflammatory markers and lipid profiles at baseline as well as 7 days, 2, 4 and 6 weeks after antibiotics.
It is estimated that a total of 10 patients in each arm are needed.
|- Main changes (audit trail)|
|- RECORD||15-okt-2010 - 26-feb-2011|