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Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome (Microbes4U)

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ClinicalTrials.gov Identifier: NCT02637115
Recruitment Status : Completed
First Posted : December 22, 2015
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Information provided by (Responsible Party):
Patrice D. Cani, Université Catholique de Louvain

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome x Glucose Metabolism Disorders Dyslipidemias Obesity Dietary Supplement: Placebo Dietary Supplement: Live Akk 9 Dietary Supplement: Live Akk 10 Dietary Supplement: Killed Akk Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking Description: Subjects and physicians were both blinded to the treatment allocation.
Primary Purpose: Basic Science
Official Title: Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome Related to Obesity
Actual Study Start Date : December 2015
Actual Primary Completion Date : February 20, 2018
Actual Study Completion Date : February 20, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo corresponds to a solution of Phosphate buffer saline (PBS) and glycerol, that is the carrier used in the 3 other groups receiving the bacteria (active arms)
Dietary Supplement: Placebo
Consumption of one dose-sachet per day. This dose-sachet contains a placebo (PBS/Glycerol)

Experimental: Live Akk 9
Live Akkermansia muciniphila (Akk) at the dose of 10exp9 live bacteria (one billion of live bacteria) per day
Dietary Supplement: Live Akk 9
Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (one billion per dose-sachet)

Experimental: Live Akk 10
Live Akkermansia muciniphila (Akk) at the dose of 10exp10 live bacteria (ten billion of live bacteria) per day
Dietary Supplement: Live Akk 10
Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (ten billion per dose-sachet)

Experimental: Killed Akk
This group corresponds to Akkermansia muciniphila that have been heat-killed. The initial quantity of bacteria before the heating procedure was of 10exp10 bacteria.
Dietary Supplement: Killed Akk
Consumption of one dose-sachet per day. This dose-sachet contains heat-killed Akkermansia muciniphila




Primary Outcome Measures :
  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 Outcome Measures :
  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



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02637115


Locations
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Belgium
Cliniques universitaires Saint-Luc
Brussels, Belgium, 1200
Sponsors and Collaborators
Patrice D. Cani
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
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Study Director: Patrice D. Cani, Professor Université Catholique de Louvain

Publications:
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Responsible Party: Patrice D. Cani, Professor, Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT02637115     History of Changes
Other Study ID Numbers: 2015/02JUL/369
B403201525111 ( Other Identifier: Université catholique de Louvain )
First Posted: December 22, 2015    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Patrice D. Cani, Université Catholique de Louvain:
Gut microbiota
Akkermansia muciniphila

Additional relevant MeSH terms:
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Obesity
Metabolic Syndrome
Dyslipidemias
Metabolic Diseases
Glucose Metabolism Disorders
Syndrome
Disease
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Lipid Metabolism Disorders