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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

Tracking Information
First Submitted Date  ICMJE December 10, 2015
First Posted Date  ICMJE December 22, 2015
Last Update Posted Date May 17, 2019
Actual Study Start Date  ICMJE December 2015
Actual Primary Completion Date February 20, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Tolerance [ Time Frame: 15 days ]
    self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)
  • Tolerance [ Time Frame: 3 months ]
    self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)
  • Concentration of urea (mg/dl) [ Time Frame: 15 days ]
    measure of urea as marker of renal function
  • Concentration of urea (mg/dl) [ Time Frame: 3 months ]
    measure of urea as marker of renal function
  • Glomerular filtration rate (mL/min/1.73m2) [ Time Frame: 15 days ]
    measure of glomerular filtration rate as marker of renal function
  • Glomerular filtration rate (mL/min/1.73m2) [ Time Frame: 3 months ]
    measure of glomerular filtration rate as marker of renal function
  • Concentration of creatinine (mg/dl) [ Time Frame: 15 days ]
    measure of creatinine as marker of renal function
  • Concentration of creatinine (mg/dl) [ Time Frame: 3 months ]
    measure of creatinine as marker of renal function
  • 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
  • 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
  • Concentration of white blood cells (10exp3/µl) [ Time Frame: 15 days ]
    measured as a marker of inflammation
  • Concentration of white blood cells (10exp3/µl) [ Time Frame: 3 months ]
    measured as a marker of inflammation
  • concentration of CRP (c-reactive protein) (mg/dl) [ Time Frame: 15 days ]
    measured as a marker of inflammation
  • concentration of CRP (c-reactive protein) (mg/dl) [ Time Frame: 3 months ]
    measured as a marker of inflammation
  • Insulin resistance [ Time Frame: 3 months ]
    HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia
  • Concentration of blood lipids [ Time Frame: 3 months ]
    Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)
  • Obesity [ Time Frame: 3 months ]
    Body weight
  • Adiposity [ Time Frame: 3 months ]
    Fat mass evaluated by bioimpedance measurements
  • Visceral adiposity [ Time Frame: 3 months ]
    Waist and hip circumference
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2015)
  • Obesity [ Time Frame: 3 months ]
    Body mass index
  • Renal function [ Time Frame: 15 days ]
    Urea, creatinin, uric acid
  • Hepatic function [ Time Frame: 15 days ]
    Liver transaminase (ALT, alanine aminotransaminase; AST, aspartate transaminase; GGT, gamma glutamyl transpeptidase). LDH, lactate dehydrogenase
  • Inflammation [ Time Frame: 15 days ]
    CRP
  • Insulin resistance [ Time Frame: 3 months ]
    HOMA (fasted glycemia and insulinemia)
  • Dyslipidemia [ Time Frame: 3 months ]
    Analysis of circulating lipids
  • Adiposity [ Time Frame: 3 months ]
    Fat mass evaluated by bioimpedance measurements
  • Visceral adiposity [ Time Frame: 3 months ]
    Waist circumference
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • 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).
  • Gut barrier function [ Time Frame: 3 months ]
    Fecal calprotectin, fecal zonulin, plasma lipopolysaccharides (LPS) binding protein (LBP)
  • Metabolic endotoxemia [ Time Frame: 3 months ]
    Plasma lipopolysaccharides (LPS) by the limulus amebocyte lysate kinetic chromogenic methodology
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2015)
  • Gut microbiota composition [ Time Frame: 3 months ]
    Metagenomic analysis of the gut bacteria and gene functions by using sequencing technology, quantitative polymerase chain reaction (qPCR).
  • Gut barrier function [ Time Frame: 3 months ]
    Fecal calprotectin, fecal zonulin, plasma lipopolysaccharides (LPS) binding protein (LBP)
  • Metabolic endotoxemia [ Time Frame: 3 months ]
    Plasma lipopolysaccharides (LPS) by the limulus amaebocyte lysate kinetic chromogenic methodology
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome
Official Title  ICMJE Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome Related to Obesity
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE
  • Metabolic Syndrome x
  • Glucose Metabolism Disorders
  • Dyslipidemias
  • Obesity
Intervention  ICMJE
  • Dietary Supplement: Placebo
    Consumption of one dose-sachet per day. This dose-sachet contains a placebo (PBS/Glycerol)
  • Dietary Supplement: Live Akk 9
    Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (one billion per dose-sachet)
  • Dietary Supplement: Live Akk 10
    Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (ten billion per dose-sachet)
  • Dietary Supplement: Killed Akk
    Consumption of one dose-sachet per day. This dose-sachet contains heat-killed Akkermansia muciniphila
Study Arms  ICMJE
  • 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)
    Intervention: Dietary Supplement: Placebo
  • Experimental: Live Akk 9
    Live Akkermansia muciniphila (Akk) at the dose of 10exp9 live bacteria (one billion of live bacteria) per day
    Intervention: Dietary Supplement: Live Akk 9
  • Experimental: Live Akk 10
    Live Akkermansia muciniphila (Akk) at the dose of 10exp10 live bacteria (ten billion of live bacteria) per day
    Intervention: Dietary Supplement: Live Akk 10
  • 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.
    Intervention: Dietary Supplement: Killed Akk
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 2, 2018)
54
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2015)
100
Actual Study Completion Date  ICMJE February 20, 2018
Actual Primary Completion Date February 20, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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%
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02637115
Other Study ID Numbers  ICMJE 2015/02JUL/369
B403201525111 ( Other Identifier: Université catholique de Louvain )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Patrice D. Cani, Université Catholique de Louvain
Study Sponsor  ICMJE Patrice D. Cani
Collaborators  ICMJE Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators  ICMJE
Study Director: Patrice D. Cani, Professor Université Catholique de Louvain
PRS Account Université Catholique de Louvain
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP