Skip to main content
OpenTrials
Completed

NCT Number: NCT02637115

Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome

Overweight and obesity have reached worldwide epidemic level. Both overweight and obesity are characterized by comorbidities such as cardio-metabolic risk factors (i.e., insulin resistance, type 2 diabetes, hypertension, dyslipidemia, low-grade inflammation) representing a major public health problem. Therefore, it is urgent to find a therapeutic solution to target all these metabolic disorders. Among the environmental factors able to influence the individual susceptibility to gain weight and to develop metabolic disorders associated with obesity, more and more evidence show that the trillions of bacteria housed in our gastro-intestinal tract (i.e, gut microbiota) influence host metabolism. The investigators recently discovered a putative interesting microbial candidate, namely Akkermansia muciniphila (Akk). More exactly, we found that the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia and inflammatory markers in diet-induced obese mice. Moreover, in overweight/obese patients with cardiovascular risk factors subjected to a calorie restriction diet (calorie restriction diet for 6 weeks and an additional 6 weeks of weight maintenance), a higher abundance of Akkermansia muciniphila was associated with a better cardio-metabolic status in these patients. The investigators also discovered that patients having more Akkermansia muciniphila in their gut before the calorie restriction exhibited a greater improvement in glucose homoeostasis, blood lipids and body composition after calorie restriction. These observations suggested that the administration of Akkermansia muciniphila in overweight or obese people could be a very interesting therapeutic solution. Currently, no human study has investigated the beneficial effects of Akkermansia muciniphila administration on obesity and metabolic disorders. The overall objective of this study is to evaluate the effects associated with the administration of live or heat-killed Akkermansia muciniphila on the metabolic disorders (insulin-resistance, type-2 diabetes, dyslipidemia, inflammation) related to overweight and obesity in humans.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Metabolic Syndrome X Body Weight Dyslipidemias Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Lipid Metabolism Disorders Metabolic Diseases Metabolic Syndrome Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Aged between 18 and 70 years old
  • Caucasian
  • Insulin resistance (based on HOMA single-value)
  • BMI between 25 and 50 kg/m²
  • Metabolic syndrome: presence of at least 3 of the following criteria
  • Hypertension (blood pressure ≥ 130/85 mm Hg or antihypertensive treatment)
  • Hypertriglyceridemia (triglyceridemia ≥ 150mg/dl)
  • Low HDL-cholesterol (HDL-cholesterol < 40mg/dl for males, 50mg/dl for females)
  • Visceral obesity (waist circumference > 102 cm for males, 88cm for females)
  • Fasting hyperglycemia (fasting glycemia ≥ 110mg/dl)
  • Informed consent signed by the patient

Exclusion criteria

  • Acute or chronic progressive or chronic unstabilized diseases
  • Alcohol consumption (more than 2 glasses per day)
  • Previous bariatric surgery
  • Surgery in the 3 months prior the study or surgery planned in the next 6 months
  • Pregnancy or pregnancy planned in the next 6 months
  • More than 30 minutes of sports 3 times per week
  • Consumption of dietary supplement (omega-3 fatty acids, probiotics, prebiotics, plant stanols/sterols) in the month prior the study
  • Inflammatory bowel disease or irritable bowel syndrome
  • Diabetic gastrointestinal autonomic neuropathy (such as gastroparesis or reduced gastrointestinal motility)
  • Consumption of more than 30g of dietary fibers per day
  • Vegetarian or unusual diet
  • Lactose intolerance or milk protein allergy
  • Gluten intolerance
  • Medications influencing parameters of interest (antidiabetic drugs such as metformin, DPP-4 inhibitors, GLP-1 receptor agonists, acarbose, hypoglycemic sulfonamides,glinides, thiazolidinediones, SGLT2 inhibitors, insulin,lactulose, consumption of antibiotics in the 2 months prior the study, corticosteroids, immunosuppressive agents, statins, fibrate, orlistat, cholestyramine, ezetimibe)
  • Glycated hemoglobin (HbA1c) > 7.5%

Treatment and study plan

Placebo

Dietary Supplement

Consumption of one dose-sachet per day. This dose-sachet contains a placebo (PBS/Glycerol)

Live Akk 9

Dietary Supplement

Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (one billion per dose-sachet)

Live Akk 10

Dietary Supplement

Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (ten billion per dose-sachet)

Killed Akk

Dietary Supplement

Consumption of one dose-sachet per day. This dose-sachet contains heat-killed Akkermansia muciniphila

Primary outcomes

  1. Tolerance

    Time frame: 15 days

    self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)

  2. Tolerance

    Time frame: 3 months

    self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)

  3. Concentration of urea (mg/dl)

    Time frame: 15 days

    measure of urea as marker of renal function

  4. Concentration of urea (mg/dl)

    Time frame: 3 months

    measure of urea as marker of renal function

  5. Glomerular filtration rate (mL/min/1.73m2)

    Time frame: 15 days

    measure of glomerular filtration rate as marker of renal function

  6. Glomerular filtration rate (mL/min/1.73m2)

    Time frame: 3 months

    measure of glomerular filtration rate as marker of renal function

  7. Concentration of creatinine (mg/dl)

    Time frame: 15 days

    measure of creatinine as marker of renal function

  8. Concentration of creatinine (mg/dl)

    Time frame: 3 months

    measure of creatinine as marker of renal function

  9. Concentration of liver transaminases

    Time frame: 15 days

    measure of alanine aminotransferase (U/L); aspartate aminotransferase (U/L); gamma glutamyl transpeptidase (U/L). Lactate dehydrogenase (UI/L) as markers of hepatic inflammation

  10. Concentration of liver transaminases

    Time frame: 3 months

    measure of alanine aminotransferase (U/L); aspartate aminotransferase (U/L); gamma glutamyl transpeptidase (U/L). Lactate dehydrogenase (UI/L) as markers of hepatic inflammation

  11. Concentration of white blood cells (10exp3/µl)

    Time frame: 15 days

    measured as a marker of inflammation

  12. Concentration of white blood cells (10exp3/µl)

    Time frame: 3 months

    measured as a marker of inflammation

  13. concentration of CRP (c-reactive protein) (mg/dl)

    Time frame: 15 days

    measured as a marker of inflammation

  14. concentration of CRP (c-reactive protein) (mg/dl)

    Time frame: 3 months

    measured as a marker of inflammation

  15. Insulin resistance

    Time frame: 3 months

    HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia

  16. Concentration of blood lipids

    Time frame: 3 months

    Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)

  17. Obesity

    Time frame: 3 months

    Body weight

  18. Adiposity

    Time frame: 3 months

    Fat mass evaluated by bioimpedance measurements

  19. Visceral adiposity

    Time frame: 3 months

    Waist and hip circumference

Secondary outcomes

  1. Measure of the concentration of Akkermansia in the feces (bacterial cells/g of feces)

    Time frame: 3 months

    Metagenomic analysis of the gut bacteria by using sequencing technology and by using quantitative polymerase chain reaction (qPCR).

  2. Gut barrier function

    Time frame: 3 months

    Fecal calprotectin, fecal zonulin, plasma lipopolysaccharides (LPS) binding protein (LBP)

  3. Metabolic endotoxemia

    Time frame: 3 months

    Plasma lipopolysaccharides (LPS) by the limulus amebocyte lysate kinetic chromogenic methodology

  4. Gut microbial-related metabolites in urine

    Time frame: 3 months

    Metabolomic analysis of the bacterial metabolites present in the urine by combining nuclear magnetic resonance (1H-NMR) and mass spectrometry

  5. Gut microbial-related metabolites in plasma

    Time frame: 3 months

    Metabolomic analysis of the bacterial metabolites present in the plasma by combining nuclear magnetic resonance (1H-NMR) and mass spectrometry

Sponsors and collaborators

Lead sponsor

Patrice D. Cani

Other

Collaborators

  • Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Registry information

Official study title

Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome Related to Obesity

Acronym: Microbes4U

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
Dec 22, 2015
Registry last updated
May 17, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.