The Importance of the Gut Microbiota in Body Weight Control and Insulin Sensitivity

NCT02241421 | Completed

• 1 other identifier: 11-3-072
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity; Insulin Resistance

Keywords

Impaired glucose tolerance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Lipid metabolism; Anti Bacterial Agents; Gastro Intestinal Tract

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity

  Before and after the intervention, insulin sensitivity will be measured by using the hyperinsulinemic-euglycemic clamp technique including a glucose tracer to accurately quantify glucose fluxes at the whole body level. Glucose and Insulin levels will be determined.

  up to two weeks

Secondary Outcomes (5)

• Fatty Acid Handling in the muscle

  up to two weeks

• Markers of inflammation

  up to two weeks

• Energy expenditure

  up to two weeks

• Microbiota composition and energy content in faecal samples

  up to two weeks

• Gut wall permeability

  up to two weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

No intervention: Placebo 3x2 capsules per day during 7 consecutive days.

Other: Placebo

Treatment Antibiotics: Amoxicillin

EXPERIMENTAL

Experimental: Amoxicillin (broad spectrum antibiotics) 1500 mg/day (3x2 capsules of 250 mg) during 7 consecutive days.

Drug: Amoxicillin

Treatment Antibiotics: Vancomycin

EXPERIMENTAL

Experimental: Vancomycin (small spectrum antibiotics) 1500mg/day (3x2 capsules of 250 mg) during 7 consecutive days

Drug: Vancomycin

Interventions

Amoxicillin DRUG

Treatment Antibiotics: Amoxicillin

Vancomycin DRUG

Also known as: Vancocin CP 250

Treatment Antibiotics: Vancomycin

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male
• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Top Institute Food and Nutrition: collaborator

Study Sites (1)

Maastricht University

Maastricht, Netherlands

Location

Related Publications (2)

• Reijnders D, Goossens GH, Hermes GDA, Smidt H, Zoetendal EG, Blaak EE. Short-Term Microbiota Manipulation and Forearm Substrate Metabolism in Obese Men: A Randomized, Double-Blind, Placebo-Controlled Trial. Obes Facts. 2018;11(4):318-326. doi: 10.1159/000492114. Epub 2018 Aug 9.

  PMID: 30089301 DERIVED

• Jocken JWE, Reijnders D, Canfora EE, Boekschoten MV, Plat J, Goossens GH, Blaak EE. Effects of gut microbiota manipulation on ex vivo lipolysis in human abdominal subcutaneous adipocytes. Adipocyte. 2018;7(2):106-112. doi: 10.1080/21623945.2018.1464366. Epub 2018 Apr 25.

  PMID: 29693476 DERIVED

MeSH Terms

Conditions

Obesity; Insulin Resistance; Glucose Intolerance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Interventions

Amoxicillin; Vancomycin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperglycemia

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Ellen E Blaak, Prof.Dr.

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: September 16, 2014
• Study Start: April 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: September 10, 2020

Record last verified: 2020-09

Locations

NL (1)