Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome Related to Obesity
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- concentration of CRP (c-reactive protein) (mg/dl)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Care Provider)
Masking Description
Subjects and physicians were both blinded to the treatment allocation.
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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%
Arms & Interventions
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: Placebo (Dietary Supplement)
Live Akk 9
Live Akkermansia muciniphila (Akk) at the dose of 10exp9 live bacteria (one billion of live bacteria) per day
Intervention: Live Akk 9 (Dietary Supplement)
Live Akk 10
Live Akkermansia muciniphila (Akk) at the dose of 10exp10 live bacteria (ten billion of live bacteria) per day
Intervention: Live Akk 10 (Dietary Supplement)
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: Killed Akk (Dietary Supplement)
Outcomes
Primary Outcomes
concentration of CRP (c-reactive protein) (mg/dl)
Time Frame: 3 months
measured as a marker of inflammation
Tolerance
Time Frame: 3 months
self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)
Glomerular filtration rate (mL/min/1.73m2)
Time Frame: 3 months
measure of glomerular filtration rate as marker of renal function
Concentration of urea (mg/dl)
Time Frame: 3 months
measure of urea 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: 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: 3 months
measured as a marker of inflammation
Insulin resistance
Time Frame: 3 months
HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia
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
Concentration of blood lipids
Time Frame: 3 months
Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)
Concentration of creatinine (mg/dl)
Time Frame: 15 days
measure of creatinine as marker of renal function
Tolerance
Time Frame: 15 days
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
Glomerular filtration rate (mL/min/1.73m2)
Time Frame: 15 days
measure of glomerular filtration rate 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 white blood cells (10exp3/µl)
Time Frame: 15 days
measured as a marker of inflammation
concentration of CRP (c-reactive protein) (mg/dl)
Time Frame: 15 days
measured as a marker of inflammation
Secondary Outcomes
- Metabolic endotoxemia(3 months)
- Gut barrier function(3 months)
- Measure of the concentration of Akkermansia in the feces (bacterial cells/g of feces)(3 months)
- Gut microbial-related metabolites in urine(3 months)
- Gut microbial-related metabolites in plasma(3 months)
Investigators
Patrice D. Cani
Professor
Université Catholique de Louvain