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

Obesity Clinical Trial

— Microbes4U  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02637115
• Other study ID #: 2015/02JUL/369
• Secondary ID: B403201525111
• Status: Completed
• Phase: N/A
• Start date: December 2015
• Est. completion date: February 20, 2018

Study information

• Verified date: May 2019
• Source: Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 20, 2018
• Est. primary completion date: February 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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%

Related Conditions & MeSH terms

• Dyslipidemias
• Glucose Metabolism Disorders
• Metabolic Diseases
• Metabolic Syndrome
• Metabolic Syndrome x
• Obesity
• Syndrome

Intervention

Dietary Supplement:
• Placebo
Consumption of one dose-sachet per day. This dose-sachet contains a placebo (PBS/Glycerol)
• Live Akk 9
Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (one billion per dose-sachet)
• Live Akk 10
Consumption of one dose-sachet per day. This dose-sachet contains Live Akkermansia muciniphila (ten billion per dose-sachet)
• Killed Akk
Consumption of one dose-sachet per day. This dose-sachet contains heat-killed Akkermansia muciniphila

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Patrice D. Cani	Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

References & Publications (3)

Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, Kayser BD, Levenez F, Chilloux J, Hoyles L; MICRO-Obes Consortium, Dumas ME, Rizkalla SW, Doré J, Cani PD, Clément K. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016 Mar;65(3):426-36. doi: 10.1136/gutjnl-2014-308778. Epub 2015 Jun 22. — View Citation

Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013 May 28;110(22):9066-71. doi: 10.1073/pnas.1219451110. Epub 2013 May 13. — View Citation

Schneeberger M, Everard A, Gómez-Valadés AG, Matamoros S, Ramírez S, Delzenne NM, Gomis R, Claret M, Cani PD. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep. 2015 Nov 13;5:16643. doi: 10.1038/srep16643. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerance	self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)	15 days
Primary	Tolerance	self reporting of gastrointestinal symptoms (nausea, bloating, flatulence, cramp, borborygmi and gastric reflux)	3 months
Primary	Concentration of urea (mg/dl)	measure of urea as marker of renal function	15 days
Primary	Concentration of urea (mg/dl)	measure of urea as marker of renal function	3 months
Primary	Glomerular filtration rate (mL/min/1.73m2)	measure of glomerular filtration rate as marker of renal function	15 days
Primary	Glomerular filtration rate (mL/min/1.73m2)	measure of glomerular filtration rate as marker of renal function	3 months
Primary	Concentration of creatinine (mg/dl)	measure of creatinine as marker of renal function	15 days
Primary	Concentration of creatinine (mg/dl)	measure of creatinine as marker of renal function	3 months
Primary	Concentration of liver transaminases	measure of alanine aminotransferase (U/L); aspartate aminotransferase (U/L); gamma glutamyl transpeptidase (U/L). Lactate dehydrogenase (UI/L) as markers of hepatic inflammation	15 days
Primary	Concentration of liver transaminases	measure of alanine aminotransferase (U/L); aspartate aminotransferase (U/L); gamma glutamyl transpeptidase (U/L). Lactate dehydrogenase (UI/L) as markers of hepatic inflammation	3 months
Primary	Concentration of white blood cells (10exp3/µl)	measured as a marker of inflammation	15 days
Primary	Concentration of white blood cells (10exp3/µl)	measured as a marker of inflammation	3 months
Primary	concentration of CRP (c-reactive protein) (mg/dl)	measured as a marker of inflammation	15 days
Primary	concentration of CRP (c-reactive protein) (mg/dl)	measured as a marker of inflammation	3 months
Primary	Insulin resistance	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia	3 months
Primary	Concentration of blood lipids	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)	3 months
Primary	Obesity	Body weight	3 months
Primary	Adiposity	Fat mass evaluated by bioimpedance measurements	3 months
Primary	Visceral adiposity	Waist and hip circumference	3 months
Secondary	Measure of the concentration of Akkermansia in the feces (bacterial cells/g of feces)	Metagenomic analysis of the gut bacteria by using sequencing technology and by using quantitative polymerase chain reaction (qPCR).	3 months
Secondary	Gut barrier function	Fecal calprotectin, fecal zonulin, plasma lipopolysaccharides (LPS) binding protein (LBP)	3 months
Secondary	Metabolic endotoxemia	Plasma lipopolysaccharides (LPS) by the limulus amebocyte lysate kinetic chromogenic methodology	3 months
Secondary	Gut microbial-related metabolites in urine	Metabolomic analysis of the bacterial metabolites present in the urine by combining nuclear magnetic resonance (1H-NMR) and mass spectrometry	3 months
Secondary	Gut microbial-related metabolites in plasma	Metabolomic analysis of the bacterial metabolites present in the plasma by combining nuclear magnetic resonance (1H-NMR) and mass spectrometry	3 months