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Effect of Pasteurized Akkermansia Muciniphila on Insulin Resistance in Otherwise Healthy Subjects With Dysglycaemia

Primary Purpose

Metabolic Syndrome, Pre-diabetes, Overweight and Obesity

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Pasteurized A. muciniphila
placebo
Sponsored by
A-Mansia Biotech S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metabolic Syndrome

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Written informed consent;
  • BMI between >25 and <40 Kg/m2;
  • Qualifying for the diagnosis of metabolic syndrome according to the International Diabetes Federation (IDF 2006) criteria. At least any three of five citeria, with the modification that the criterion FPG≥100 mg/dL (5.6 mmol/L) is required among at least three of five:

    • Increased waist circumference: for Europid, sub-Saharan African, Eastern and Middle-Eastern ≥94 cm (men) or ≥80 cm (women), with ethnic-specific waist circumference cut-points: for South Asian and Chinese patients, waist ≥90 cm (men) or ≥80 cm (women); for Japanese patients, waist ≥90 cm (men) or ≥80 cm (women);
    • Triglycerides ≥150 mg/dL (1.7 mmol/L) (exception: triglycerides ≥100 mg/dL (1.13mmol/L) for sub-Saharan African) or treatment for elevated triglycerides;
    • HDL cholesterol <40 mg/dL (1.03 mmol/L) in men or <50 mg/dL (1.29 mmol/L) in females, or treatment for low HDL;
    • Systolic blood pressure ≥130, diastolic blood pressure ≥85 mmHg, or treatment for hypertension;
    • FPG ≥100 mg/dL (5.6 mmol/L) or previously diagnosed type 2 diabetes; an oral glucose tolerance test is recommended for patients with an elevated FPG, but it is not required.
  • If participant has a prior diagnosis of pre-diabetes or Type II diabetes, and has been unmedicated for 3-months prior to screening;
  • If female, must meet all the following criteria:

    • Not pregnant or breastfeeding
    • If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectable or oral contraceptives [must have been using for at least the last 3 months], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized partner) during the entire duration of the study
  • Be willing to maintain stable dietary habits and physical activity levels throughout the trial period;
  • Be able to communicate well with the Investigator, to understand and comply with the requirements of the study and be judged suitable for the study in the opinion of the Investigator.

Within 3 months following to the exit of the study for failure to comply with one or more of the inclusion criteria listed above, a re-screening could be performed.

Exclusion Criteria:

  • Uncontrolled hyperglycemia assessed by HbA1c ≥ 6.5%;
  • Suffering from a metabolic disorder such as diabetes mellitus that requires lifesyle and dietary recommendations or a medication according to the recommendations, uncontrolled thyroidal trouble (Confirmed by clinical significant abnormal TSG/T4 and/or stabled medication for >3 months) or other metabolic disorder;
  • Suffering from a severe chronic disease (e.g., cancer, HIV, renal failure, hepatic or biliary disorders ongoing, chronic inflammatory digestive disease, inflammatory bowel disease, irritable bowel syndrome, arthritis or other chronic respiratory trouble, etc.) or gastrointestinal disorders found to be inconsistent with the conduct of the study by the investigator (e.g., celiac disease);
  • With a history of retinopathy, microalbuminuria, ischemic cardiovascular event during the previous 6 months;
  • Consumption of more than 30 g of dietary fibre per day, as measured by the Block Fibre Screener
  • Prior diagnosis of Type I diabetes mellitus (i.e., a clinical diagnosis made before the screening visit of this study);
  • Alcohol consumption (>21 units per week);
  • Smoking more than 10 cigarettes per day;
  • Previous bariatric surgery;
  • Any surgery in the 3 months before the study or planned for 6 months after enrolling;
  • Pregnancy or pregnancy planned in the 6 months after enrolling or lactating women;
  • Consumption of dietary supplements (omega-3 fatty acids, probiotics, prebiotics, plant stanols/sterols) in the 4-weeks before the study;
  • Presence or history of significant and diagnosed gastrointestinal diseases that, in the opinion of the investigator, could be associated with disturbed gastrointestinal absorption (e.g., resections, diverticula, active and diagnostically confirmed irritable bowel syndrome, malabsorption syndrome);
  • Present or recent (within 3-months of screening) use of any other medication which, in the opinion of the investigator, could interfere with the outcome of the study, including but not limited to antithrombotic agents, anti-inflammatory agents and chronic NSAID use (except low-dose prophylactic, proton pump inhibitors (PPIs), antihistamines, if ongoing (3-months) and on a stable dose throughout study period);
  • Steroids (over the counter (OTC) NSAIDS, topical steroids and inhalers are allowed)
  • Current or planned participation in a weight-loss regimen (including intermediate fasting), including extreme dietary practices or exercise;
  • Anorexia nervosa, bulimia or significant eating disorders according to the investigators;
  • Having lost >5% of their body weight within 3-months prior to screening;
  • Lactose intolerance or milk protein allergy;
  • Gluten intolerance;
  • Current treatment with medications influencing the parameters of interest (glucose-lowering drugs such as metformin, DPP4 inhibitors, GLP-1 receptor agonists, acarbose, sulfonylureas, glinides, thiazolidinediones, sodium-glucose cotransporter -2 inhibitors, insulin, lactulose, glucocorticoids, immunosuppressive agents, , orlistat, cholestyramine or ezetimibe);
  • Antibiotic use in the 3 months before the study;
  • Participant has a known allergy to inactive or active ingredients in the study products;
  • Participation in other clinical research trials within 90 days prior to randomization;
  • Any other condition which in the Investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may pose significant risk to the subject.

Sites / Locations

  • Clinical Research Center (CRC) Kiel GmbH
  • Atlantia Food Clinical Trials

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental group receiving pasteurized Akkermansia muciniphila

Control group

Arm Description

Experimental group receiving pasteurized Akkermansia muciniphila.

Control group receiving placebo, identical to verum regarding the form, size, taste, color and intake.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
fasting blood glucose
change in treatment group as compared to placebo
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
Peak Plasma Concentration (Cmax) of blood glucose as measured by OGTT
change in treatment group as compared to placebo
3-hour blood insulin incremental Area Under the Curve (AUC) as measured by OGTT
change in treatment group as compared to placebo
Peak Plasma Concentration (Cmax) of blood insulin as measured by OGTT
change in treatment group as compared to placebo
Glycosylated hemoglobin (HbA1c)
change in treatment group as compared to placebo
Postprandial triglyceride (TG) response as incremental Area Under the Curve (AUC) as measured by OGTT
change in treatment group as compared to placebo
Peak Plasma Concentration (Cmax) of blood TG as measured by OGTT
change in treatment group as compared to placebo
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
Liver enzymes (ALT, AST, GGT, bilirubin, alkaline phosphatase)
change in treatment group as compared to placebo
Anthropometry by Height (m) and body weight (kg) combined into BMI (kg/m2)
change in treatment group as compared to placebo
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
Body composition by measurement of body fat mass by DEXA measurement
change in treatment group as compared to placebo
Body composition by measurement of lean mass by DEXA measurement
change in treatment group as compared to placebo
Body composition by measurement of trunk fat mass by DEXA measurement
change in treatment group as compared to placebo
Vital signs: heart rate
evaluation of heart rate
Vital signs: blood pressure
evaluation of Systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg)
Vital signs: body temperature
evaluation of body temperature
Vital signs: respiratory rate
evaluation of respiratory rate
Adverse events
evaluation of occurrence of the nature, frequency, severity and relatedness of adverse events as well as clinically significant laboratory values

Full Information

First Posted
October 7, 2021
Last Updated
September 12, 2023
Sponsor
A-Mansia Biotech S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT05114018
Brief Title
Effect of Pasteurized Akkermansia Muciniphila on Insulin Resistance in Otherwise Healthy Subjects With Dysglycaemia
Official Title
A Randomized, Double-blind, Placebo-controlled Study to Investigate the Effects of 'Next Generation Beneficial Microbes', Akkermansia Muciniphila (AMF-01), on Long-term Improvements in Insulin Resistance in Otherwise Healthy Hyperglycaemic Adults
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 24, 2020 (Actual)
Primary Completion Date
July 28, 2023 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
A-Mansia Biotech S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome, Pre-diabetes, Overweight and Obesity

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
randomized, double-blind, placebo-controlled, parallel group, multi-center trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
144 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental group receiving pasteurized Akkermansia muciniphila
Arm Type
Experimental
Arm Description
Experimental group receiving pasteurized Akkermansia muciniphila.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Control group receiving placebo, identical to verum regarding the form, size, taste, color and intake.
Intervention Type
Dietary Supplement
Intervention Name(s)
Pasteurized A. muciniphila
Intervention Description
Daily oral dose
Intervention Type
Dietary Supplement
Intervention Name(s)
placebo
Intervention Description
Placebo = identical to verum regarding the form, size, taste, color and intake
Primary Outcome Measure Information:
Title
Insulin sensitivity by Matsuda Index
Description
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
Secondary Outcome Measure Information:
Title
Insulin sensitivity by homeostasis model assessment-estimated (HOMA) insuline sensitivity
Description
change in treatment group as compared to placebo by measuring fasting glucose and insulin values
Time Frame
From baseline to day 120
Title
fasting blood glucose
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
3-hour blood glucose incremental Area Under the Curve (AUC) as measured by Oral Glucose Tolerance Test (OGTT)
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Peak Plasma Concentration (Cmax) of blood glucose as measured by OGTT
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
3-hour blood insulin incremental Area Under the Curve (AUC) as measured by OGTT
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Peak Plasma Concentration (Cmax) of blood insulin as measured by OGTT
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Glycosylated hemoglobin (HbA1c)
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Postprandial triglyceride (TG) response as incremental Area Under the Curve (AUC) as measured by OGTT
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Peak Plasma Concentration (Cmax) of blood TG as measured by OGTT
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Blood lipid profile by total cholesterol, TG, low density lipoprotein, high density lipoprotein, non-esterified fatty acids
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Liver enzymes (ALT, AST, GGT, bilirubin, alkaline phosphatase)
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Anthropometry by Height (m) and body weight (kg) combined into BMI (kg/m2)
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
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)
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Body composition by measurement of body fat mass by DEXA measurement
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Body composition by measurement of lean mass by DEXA measurement
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Body composition by measurement of trunk fat mass by DEXA measurement
Description
change in treatment group as compared to placebo
Time Frame
From baseline to day 120
Title
Vital signs: heart rate
Description
evaluation of heart rate
Time Frame
From baseline to day 120
Title
Vital signs: blood pressure
Description
evaluation of Systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg)
Time Frame
From baseline to day 120
Title
Vital signs: body temperature
Description
evaluation of body temperature
Time Frame
From baseline to day 120
Title
Vital signs: respiratory rate
Description
evaluation of respiratory rate
Time Frame
From baseline to day 120
Title
Adverse events
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Written informed consent; BMI between >25 and <40 Kg/m2; Qualifying for the diagnosis of metabolic syndrome according to the International Diabetes Federation (IDF 2006) criteria. At least any three of five citeria, with the modification that the criterion FPG≥100 mg/dL (5.6 mmol/L) is required among at least three of five: Increased waist circumference: for Europid, sub-Saharan African, Eastern and Middle-Eastern ≥94 cm (men) or ≥80 cm (women), with ethnic-specific waist circumference cut-points: for South Asian and Chinese patients, waist ≥90 cm (men) or ≥80 cm (women); for Japanese patients, waist ≥90 cm (men) or ≥80 cm (women); Triglycerides ≥150 mg/dL (1.7 mmol/L) (exception: triglycerides ≥100 mg/dL (1.13mmol/L) for sub-Saharan African) or treatment for elevated triglycerides; HDL cholesterol <40 mg/dL (1.03 mmol/L) in men or <50 mg/dL (1.29 mmol/L) in females, or treatment for low HDL; Systolic blood pressure ≥130, diastolic blood pressure ≥85 mmHg, or treatment for hypertension; FPG ≥100 mg/dL (5.6 mmol/L) or previously diagnosed type 2 diabetes; an oral glucose tolerance test is recommended for patients with an elevated FPG, but it is not required. If participant has a prior diagnosis of pre-diabetes or Type II diabetes, and has been unmedicated for 3-months prior to screening; If female, must meet all the following criteria: Not pregnant or breastfeeding If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectable or oral contraceptives [must have been using for at least the last 3 months], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized partner) during the entire duration of the study Be willing to maintain stable dietary habits and physical activity levels throughout the trial period; Be able to communicate well with the Investigator, to understand and comply with the requirements of the study and be judged suitable for the study in the opinion of the Investigator. Within 3 months following to the exit of the study for failure to comply with one or more of the inclusion criteria listed above, a re-screening could be performed. Exclusion Criteria: Uncontrolled hyperglycemia assessed by HbA1c ≥ 6.5%; Suffering from a metabolic disorder such as diabetes mellitus that requires lifesyle and dietary recommendations or a medication according to the recommendations, uncontrolled thyroidal trouble (Confirmed by clinical significant abnormal TSG/T4 and/or stabled medication for >3 months) or other metabolic disorder; Suffering from a severe chronic disease (e.g., cancer, HIV, renal failure, hepatic or biliary disorders ongoing, chronic inflammatory digestive disease, inflammatory bowel disease, irritable bowel syndrome, arthritis or other chronic respiratory trouble, etc.) or gastrointestinal disorders found to be inconsistent with the conduct of the study by the investigator (e.g., celiac disease); With a history of retinopathy, microalbuminuria, ischemic cardiovascular event during the previous 6 months; Consumption of more than 30 g of dietary fibre per day, as measured by the Block Fibre Screener Prior diagnosis of Type I diabetes mellitus (i.e., a clinical diagnosis made before the screening visit of this study); Alcohol consumption (>21 units per week); Smoking more than 10 cigarettes per day; Previous bariatric surgery; Any surgery in the 3 months before the study or planned for 6 months after enrolling; Pregnancy or pregnancy planned in the 6 months after enrolling or lactating women; Consumption of dietary supplements (omega-3 fatty acids, probiotics, prebiotics, plant stanols/sterols) in the 4-weeks before the study; Presence or history of significant and diagnosed gastrointestinal diseases that, in the opinion of the investigator, could be associated with disturbed gastrointestinal absorption (e.g., resections, diverticula, active and diagnostically confirmed irritable bowel syndrome, malabsorption syndrome); Present or recent (within 3-months of screening) use of any other medication which, in the opinion of the investigator, could interfere with the outcome of the study, including but not limited to antithrombotic agents, anti-inflammatory agents and chronic NSAID use (except low-dose prophylactic, proton pump inhibitors (PPIs), antihistamines, if ongoing (3-months) and on a stable dose throughout study period); Steroids (over the counter (OTC) NSAIDS, topical steroids and inhalers are allowed) Current or planned participation in a weight-loss regimen (including intermediate fasting), including extreme dietary practices or exercise; Anorexia nervosa, bulimia or significant eating disorders according to the investigators; Having lost >5% of their body weight within 3-months prior to screening; Lactose intolerance or milk protein allergy; Gluten intolerance; Current treatment with medications influencing the parameters of interest (glucose-lowering drugs such as metformin, DPP4 inhibitors, GLP-1 receptor agonists, acarbose, sulfonylureas, glinides, thiazolidinediones, sodium-glucose cotransporter -2 inhibitors, insulin, lactulose, glucocorticoids, immunosuppressive agents, , orlistat, cholestyramine or ezetimibe); Antibiotic use in the 3 months before the study; Participant has a known allergy to inactive or active ingredients in the study products; Participation in other clinical research trials within 90 days prior to randomization; Any other condition which in the Investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may pose significant risk to the subject.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Suenaert, MD, PhD
Organizational Affiliation
R&D and Clinical Development
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Research Center (CRC) Kiel GmbH
City
Kiel
Country
Germany
Facility Name
Atlantia Food Clinical Trials
City
Cork
Country
Ireland

12. IPD Sharing Statement

Citations:
PubMed Identifier
31263284
Citation
Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, de Barsy M, Loumaye A, Hermans MP, Thissen JP, de Vos WM, Cani PD. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019 Jul;25(7):1096-1103. doi: 10.1038/s41591-019-0495-2. Epub 2019 Jul 1.
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Effect of Pasteurized Akkermansia Muciniphila on Insulin Resistance in Otherwise Healthy Subjects With Dysglycaemia

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