This trial is active, not recruiting.

Conditions obesity, insulin resistance
Treatments amoxicillin, vancomycin
Sponsor Maastricht University Medical Center
Collaborator Top Institute Food and Nutrition
Start date April 2012
End date October 2014
Trial size 57 participants
Trial identifier NCT02241421, 11-3-072


BACKGROUND: The relation between gut microbiota and obesity originates from animal studies, showing that the change of gut microbiota can induce changes in both insulin resistance and body composition. In addition, these studies have shown changes in gut permeability inducing a pro-inflammatory state, changes in adipose tissue function and inflammation, effects on energy harvesting and metabolism, skeletal muscle fatty acid partitioning and fat oxidation. Human data is lacking, although several studies suggested that the composition of the gut microbiota differs between lean and obese, and between diabetic and non-diabetic individuals.

OBJECTIVE: To provide insight in the physiological significance and underlying mechanisms involved in the relation between gut microbiota, energy balance and insulin sensitivity in overweight men with impaired glucose homeostasis.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose basic science
(Placebo Comparator)
No intervention: Placebo 3x2 capsules per day during 7 consecutive days.
Experimental: Amoxicillin (broad spectrum antibiotics) 1500 mg/day (3x2 capsules of 250 mg) during 7 consecutive days.
Experimental: Vancomycin (small spectrum antibiotics) 1500mg/day (3x2 capsules of 250 mg) during 7 consecutive days
vancomycin Vancocin CP 250

Primary Outcomes

Insulin sensitivity
time frame: up to two weeks

Secondary Outcomes

Fatty Acid Handling in the muscle
time frame: up to two weeks
Markers of inflammation
time frame: up to two weeks
Energy expenditure
time frame: up to two weeks
Microbiota composition and energy content in faecal samples
time frame: up to two weeks
Gut wall permeability
time frame: up to two weeks

Eligibility Criteria

Male participants from 35 years up to 70 years old.

Inclusion Criteria: - male - 35-70 years - caucasian - overweight/obese (BMI 25-35 kg/m2) - insulin resistant (Homeostasis Model of Assessment - Insulin Resistance (HOMA_IR) > 2.2) - impaired glucose tolerance (IGT: 2h plasma glucose during 75g Oral Glucose Tolerance Test(OGTT) 7.8-11.1 mmol/l) and/or impaired fasting glucose (plasma glucose ≥ 5.6 mmol/l) - body weight stable for at least three months (±3 kg) Exclusion Criteria: - known allergic reaction to vancomycin, teicoplanin, amoxicillin and other β-lactam antibiotics (penicillins and cefalosporins) or related antibiotics - diabetes mellitus - hearing disorders - cardiovascular disease - kidney disease - gastrointestinal disease - cancer - asthma or bronchitis - liver malfunction - major illness with a life expectancy < 5 years - diseases affecting glucose tolerance (e.g. pheochromocytoma, Cushing's syndrome, acromegaly), - - use of antibiotics in the past 3 months - plans to lose weight and participation in organized sports activities for >3 hours per week - The use of β-blockers, lipid lowering-drugs, glucose-lowering agents (including all sulfonylureas, biguanides, α-glucosidase inhibitors, thiazolidinediones, repaglinide, nateglinide and insulin), anti-oxidants or chronic corticosteroids treatment (> 7 consecutive days of treatment)

Additional Information

Official title The Effect of the Knock Down of Gut Microbiota by Antibiotics on Parameters of Body Weight Control and Insulin Sensitivity
Principal investigator Ellen E Blaak, Prof.Dr.
Description The view on the putative significance of gut microbiota in metabolism emerged from animal studies. Bäcked et al. showed that germ free mice had 40% less body fat compared to conventionally raised mice. Transplantation of a cecum-derived microbial community of conventional mice into germ free mice, resulted in a significant increase of body weight and insulin resistance within 2 weeks. Application of metagenomic techniques in leptin-deficient ob/ob mice showed a different proportion of bacteria belonging when compared to lean, wild-type or heterozygous mice, with a greater representation of Firmicutes and fewer Bacteroidetes. This obese gut microbiome showed an enrichment in genes involved in energy extraction from food, less energy left over in the faeces and higher contents of the short-chain fatty acids (SCFAs) propionate, acetate and butyrate in the cecum. Furthermore, microbiota composition may alter gut permeability, and may play a role in the development of metabolic endotoxemia (inflammation) and related impairments in glucose metabolism. In addition, the gut microbiota may determine AMP-activated protein kinase (AMPK) levels in muscle and liver, thereby affecting fatty acid oxidation (substrate metabolism) and fat storage. However, underlying mechanisms are not completely understood. Therefore, researchers within the Top Institute Food and Nutrition (TIFN) have designed a multidisciplinary project ('Microbiota, energy balance and metabolism'), to fill the unmet gap between gut microbiota and human energy metabolism. The current protocol is designed to clarify the role of the gut microbiota in host energy metabolism and insulin sensitivity, with the main focus on underlying mechanisms.
Trial information was received from ClinicalTrials.gov and was last updated in September 2014.
Information provided to ClinicalTrials.gov by Maastricht University Medical Center.