The purpose of this study is to demonstrate the efficacy of pasteurized Akkermansia muciniphila (pAKK) in improving insulin sensitivity in hyperglycaemic, but otherwise healthy persons with metabolic syndrome. This is the primary objective of this study. Secondary objectives consist of evaluation of the effects of next generation beneficial microbes on metabolic health, anthropometry and body composition, and safety. Therefore, the trial is designed as a phase 2, randomized, double-blind, placebo-controlled, parallel group, multi-center trial comparing pAKK with placebo in restoring insulin sensitivity in dysglycaemic but otherwise healthy subjects with metabolic syndrome. In total, 144 enrolled participants will attend 6 study visits in total. Study visits may be conducted in the clinic, at home by a Healthcare Professional, or by telephone / telemedicine.
Overweight and obesity have reached worldwide epidemic level. Observation of elevated glycaemia like impaired fasting glucose and impaired glucose tolerance are reflecting pre-diabetic states often occurring in the context of development of insulin resistance in persons with metabolic syndrome. Moreover, this status is associated with the risk for developing type 2 diabetes as well as cardiovascular disease. In a proof of concept study the supplementation with A. muciniphila was safe and improved metabolic health in persons with metabolic syndrome. The purpose of this study is to demonstrate the efficacy of pasteurized Akkermansia muciniphila (pAKK) in improving insulin sensitivity in hyperglycaemic, but otherwise healthy persons with metabolic syndrome. This is the primary objective of this study. Secondary objectives consist of evaluation of the effects of next generation beneficial microbes on metabolic health, anthropometry and body composition, and safety. Therefore, the trial is designed as a phase 2, randomized, double-blind, placebo-controlled, parallel group, multi-center trial comparing pAKK with placebo in restoring insulin sensitivity in dysglycaemic but otherwise healthy subjects with metabolic syndrome. In total, 144 enrolled participants will attend 6 study visits in total. Study visits may be conducted in the clinic, at home by a Healthcare Professional, or by telephone / telemedicine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
143
Daily oral dose
Placebo = identical to verum regarding the form, size, taste, color and intake
Clinical Research Center (CRC) Kiel GmbH
Kiel, Germany
Atlantia Food Clinical Trials
Cork, Ireland
Insulin sensitivity by Matsuda Index
Absolute change from baseline to day 120 in treatment group as compared to placebo in insulin sensitivity as determined by Matsuda.
Time frame: From baseline to day 120
Insulin sensitivity by homeostasis model assessment-estimated (HOMA) insuline sensitivity
change in treatment group as compared to placebo by measuring fasting glucose and insulin values
Time frame: From baseline to day 120
fasting blood glucose
change in treatment group as compared to placebo
Time frame: From baseline to day 120
3-hour blood glucose incremental Area Under the Curve (AUC) as measured by Oral Glucose Tolerance Test (OGTT)
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Peak Plasma Concentration (Cmax) of blood glucose as measured by OGTT
change in treatment group as compared to placebo
Time frame: From baseline to day 120
3-hour blood insulin incremental Area Under the Curve (AUC) as measured by OGTT
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Peak Plasma Concentration (Cmax) of blood insulin as measured by OGTT
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Glycosylated hemoglobin (HbA1c)
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Postprandial triglyceride (TG) response as incremental Area Under the Curve (AUC) as measured by OGTT
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Peak Plasma Concentration (Cmax) of blood TG as measured by OGTT
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Blood lipid profile by total cholesterol, TG, low density lipoprotein, high density lipoprotein, non-esterified fatty acids
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Liver enzymes (ALT, AST, GGT, bilirubin, alkaline phosphatase)
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Anthropometry by Height (m) and body weight (kg) combined into BMI (kg/m2)
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Circumference (cm) of waist, hip and neck and waist, hip and height measurement will be combined into Waist-to-Hip ratio (W:H) and Waist-to-Height ratio (WHtR)
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Body composition by measurement of body fat mass by DEXA measurement
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Body composition by measurement of lean mass by DEXA measurement
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Body composition by measurement of trunk fat mass by DEXA measurement
change in treatment group as compared to placebo
Time frame: From baseline to day 120
Vital signs: heart rate
evaluation of heart rate
Time frame: From baseline to day 120
Vital signs: blood pressure
evaluation of Systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg)
Time frame: From baseline to day 120
Vital signs: body temperature
evaluation of body temperature
Time frame: From baseline to day 120
Vital signs: respiratory rate
evaluation of respiratory rate
Time frame: From baseline to day 120
Adverse events
evaluation of occurrence of the nature, frequency, severity and relatedness of adverse events as well as clinically significant laboratory values
Time frame: From baseline to day 120
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