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ObesityANTIBIOTICSNCT02241421

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

A study testing Amoxicillin and Vancomycin in people with Obesity and Insulin Resistance, run by Maastricht University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 35 to 70 years, men only
Conditions the study is for
Obesity, Insulin Resistance
What is being tested?
Amoxicillin and Vancomycin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
57 participants
Where
1 siteNetherlands
Study dates
Apr 2012to Nov 2014
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 70 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 13Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Maastricht University

    Maastricht

Other trials in Netherlands

About this study

Official title: The Effect of the Knock Down of Gut Microbiota by Antibiotics on Parameters of Body Weight Control and Insulin Sensitivity

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.

Read the detailed 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.

Being tested
Amoxicillin, Vancomycin, Placebo
Keywords
Impaired glucose tolerance, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Hyperinsulinism, Lipid metabolism, Anti Bacterial Agents, Gastro Intestinal Tract
Medical subject headings
Obesity, Insulin Resistance, Glucose Intolerance, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Hyperinsulinism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02241421
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNo intervention: Placebo 3x2 capsules per day during 7 consecutive days.
Receives: Other: Placebo
Treatment Antibiotics: AmoxicillinExperimentalExperimental: Amoxicillin (broad spectrum antibiotics) 1500 mg/day (3x2 capsules of 250 mg) during 7 consecutive days.
Receives: Drug: Amoxicillin
Treatment Antibiotics: VancomycinExperimentalExperimental: Vancomycin (small spectrum antibiotics) 1500mg/day (3x2 capsules of 250 mg) during 7 consecutive days
Receives: Drug: Vancomycin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to two weeks

Secondary outcomes (5)

  1. Fatty Acid Handling in the muscle

    Because skeletal muscle is responsible for almost 80% of insulin-stimulated glucose disposal, and comprises up to 40% of total body mass, it can be considered to be a major tissue in the etiology of insulin resistance. Therefore, it is important to study the role of skeletal muscle substrate metabolism (fatty acid handling)in the context of this study. Fatty acids, glycerol, triacylglycerol and labelled palmitate in the chylomicron fraction will be measured.

    Measured: up to two weeks

  2. Markers of inflammation

    Low-grade inflammation seems to contribute to insulin resistance in obese insulin resistant subjects. Therefore, muscle and adipose tissue expression/secretion of inflammatory molecules (i.e. TNFα, IL-6) will be measured.

    Measured: up to two weeks

  3. Energy expenditure

    Indirect calorimetry measurements will be done to determine energy expenditure (O2 and CO2). While the gut microbiota plays an important role in nutrient metabolism and energy extraction from the diet, the determination of energy expenditure and energy content in faeces will provide important insight into the role of the gut microbiota in body weight regulation.

    Measured: up to two weeks

  4. Microbiota composition and energy content in faecal samples

    The composition of bacteria in the gut will be determined before and after intervention to link the composition to the primary and other secondary parameters. The energy content in the faeces will provide insight in the energy extraction capacity of the bacteria present.

    Measured: up to two weeks

  5. Gut wall permeability

    A proposed hypothesis is that gut permeability plays an important role in the induction of inflammation in obese insulin resistant subjects. A multi-sugar whole gut permeability assay will be performed.

    Measured: up to two weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2014 (estimated)
  2. Study startApr 2012
  3. Primary completionOct 2014
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02241421
Sponsor's protocol ID
11-3-072
Acronym
ANTIBIOTICS
Status last verified
Sep 2020
First submitted
22 Oct 2012
Last updated
10 Sep 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 30089301

  • 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.

    PubMed 29693476

Questions about this trial

What is this clinical trial studying?

A study testing Amoxicillin and Vancomycin in people with Obesity and Insulin Resistance, run by Maastricht University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Insulin sensitivity (time frame: up to two weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02241421, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2020.

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