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

Not Applicable

Completed

• Conditions: Glucose Metabolism Disorders; Dyslipidemias; Obesity; Metabolic Syndrome x
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Live Akk 9; Dietary Supplement: Killed Akk; Dietary Supplement: Live Akk 10

• Registration Number: NCT02637115
• Lead Sponsor: Patrice D. Cani

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 available

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2015-12-10
• Study First Submitted QC: 2015-12-17
• Study First Posted: 2015-12-22
• Primary Completion: 2018-02-20
• Study Completion: 2018-02-20
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-15
• Last Update Posted: 2019-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

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%

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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)
Live Akk 9	Live Akk 9	Live Akkermansia muciniphila (Akk) at the dose of 10exp9 live bacteria (one billion of live bacteria) per day
Killed Akk	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.
Live Akk 10	Live Akk 10	Live Akkermansia muciniphila (Akk) at the dose of 10exp10 live bacteria (ten billion of live bacteria) per day

Primary Outcome Measures

Name	Time	Method
Obesity	3 months	Body weight
Concentration of blood lipids	3 months	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)
concentration of CRP (c-reactive protein) (mg/dl)	3 months	measured as a marker of inflammation
Tolerance	3 months	self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)
Glomerular filtration rate (mL/min/1.73m2)	3 months	measure of glomerular filtration rate as marker of renal function
Concentration of urea (mg/dl)	3 months	measure of urea as marker of renal function
Concentration of creatinine (mg/dl)	3 months	measure of creatinine as marker of renal function
Concentration of liver transaminases	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)	3 months	measured as a marker of inflammation
Insulin resistance	3 months	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia
Adiposity	3 months	Fat mass evaluated by bioimpedance measurements
Visceral adiposity	3 months	Waist and hip circumference

Secondary Outcome Measures

Name	Time	Method
Metabolic endotoxemia	3 months	Plasma lipopolysaccharides (LPS) by the limulus amebocyte lysate kinetic chromogenic methodology
Gut barrier function	3 months	Fecal calprotectin, fecal zonulin, plasma lipopolysaccharides (LPS) binding protein (LBP)
Measure of the concentration of Akkermansia in the feces (bacterial cells/g of feces)	3 months	Metagenomic analysis of the gut bacteria by using sequencing technology and by using quantitative polymerase chain reaction (qPCR).
Gut microbial-related metabolites in urine	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	3 months	Metabolomic analysis of the bacterial metabolites present in the plasma by combining nuclear magnetic resonance (1H-NMR) and mass spectrometry

Trial Locations

Locations (1)

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium