Clinical trial NCT02637115: Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome
Official title: Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome Related to Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome x
Glucose Metabolism Disorders
Dyslipidemias
Obesity
Keywords: Gut microbiota
Akkermansia muciniphila
Lead sponsor: Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
First posted: 2015-12-22
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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%

Primary outcomes:
measure: Tolerance
timeFrame: 15 days
measure: Tolerance
timeFrame: 3 months
measure: Concentration of urea (mg/dl)
timeFrame: 15 days
measure: Concentration of urea (mg/dl)
timeFrame: 3 months
measure: Glomerular filtration rate (mL/min/1.73m2)
timeFrame: 15 days
measure: Glomerular filtration rate (mL/min/1.73m2)
timeFrame: 3 months
measure: Concentration of creatinine (mg/dl)
timeFrame: 15 days
measure: Concentration of creatinine (mg/dl)
timeFrame: 3 months
measure: Concentration of liver transaminases
timeFrame: 15 days
measure: Concentration of liver transaminases
timeFrame: 3 months
measure: Concentration of white blood cells (10exp3/µl)
timeFrame: 15 days
measure: Concentration of white blood cells (10exp3/µl)
timeFrame: 3 months
measure: concentration of CRP (c-reactive protein) (mg/dl)
timeFrame: 15 days
measure: concentration of CRP (c-reactive protein) (mg/dl)
timeFrame: 3 months
measure: Insulin resistance
timeFrame: 3 months
measure: Concentration of blood lipids
timeFrame: 3 months
measure: Obesity
timeFrame: 3 months
measure: Adiposity
timeFrame: 3 months
measure: Visceral adiposity
timeFrame: 3 months
Secondary outcomes:
measure: Measure of the concentration of Akkermansia in the feces (bacterial cells/g of feces)
timeFrame: 3 months
measure: Gut barrier function
timeFrame: 3 months
measure: Metabolic endotoxemia
timeFrame: 3 months
measure: Gut microbial-related metabolites in urine
timeFrame: 3 months
measure: Gut microbial-related metabolites in plasma
timeFrame: 3 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
Study officials:
affiliation: Université Catholique de Louvain
name: Patrice D. Cani, Professor
role: STUDY_DIRECTOR
References:
citation: Schneeberger M, Everard A, Gomez-Valades AG, Matamoros S, Ramirez 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.
citation: 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, Dore J, Cani PD, Clement 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.
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.
citation: Depommier C, Vitale RM, Iannotti FA, Silvestri C, Flamand N, Druart C, Everard A, Pelicaen R, Maiter D, Thissen JP, Loumaye A, Hermans MP, Delzenne NM, de Vos WM, Di Marzo V, Cani PD. Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARalpha Agonists. Cells. 2021 Jan 19;10(1):185. doi: 10.3390/cells10010185.
citation: Depommier C, Flamand N, Pelicaen R, Maiter D, Thissen JP, Loumaye A, Hermans MP, Everard A, Delzenne NM, Di Marzo V, Cani PD. Linking the Endocannabinoidome with Specific Metabolic Parameters in an Overweight and Insulin-Resistant Population: From Multivariate Exploratory Analysis to Univariate Analysis and Construction of Predictive Models. Cells. 2021 Jan 5;10(1):71. doi: 10.3390/cells10010071.