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

NCT05114018 | Completed DMC

• 1 other identifier: AFCRO-117
• Study Type: interventional
• Target: 143
• Locations: 2 countries
• Sites: 2

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.

Conditions

Metabolic Syndrome; Pre-diabetes; Overweight and Obesity

Outcome Measures

Primary Outcomes (1)

• 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.

  From baseline to day 120

Secondary Outcomes (21)

• Insulin sensitivity by homeostasis model assessment-estimated (HOMA) insuline sensitivity

  From baseline to day 120

• fasting blood glucose

  From baseline to day 120

• 3-hour blood glucose incremental Area Under the Curve (AUC) as measured by Oral Glucose Tolerance Test (OGTT)

  From baseline to day 120

• Peak Plasma Concentration (Cmax) of blood glucose as measured by OGTT

  From baseline to day 120

• 3-hour blood insulin incremental Area Under the Curve (AUC) as measured by OGTT

  From baseline to day 120

Study Arms (2)

Experimental group receiving pasteurized Akkermansia muciniphila

EXPERIMENTAL

Experimental group receiving pasteurized Akkermansia muciniphila.

Dietary Supplement: Pasteurized A. muciniphila

Control group

PLACEBO COMPARATOR

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

Dietary Supplement: placebo

Interventions

Pasteurized A. muciniphila DIETARY_SUPPLEMENT

Daily oral dose

Experimental group receiving pasteurized Akkermansia muciniphila

placebo DIETARY_SUPPLEMENT

Placebo = identical to verum regarding the form, size, taste, color and intake

Control group

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• A-Mansia Biotech S.A.: lead

Study Sites (2)

Clinical Research Center (CRC) Kiel GmbH

Kiel, Germany

Location

Atlantia Food Clinical Trials

Cork, Ireland

Location

Related Publications (1)

• 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.

  PMID: 31263284 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Glucose Intolerance; Overweight; Obesity

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperglycemia; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Peter Suenaert, MD, PhD

  R&D and Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized, double-blind, placebo-controlled, parallel group, multi-center trial

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: November 9, 2021
• Study Start: June 24, 2020
• Primary Completion: July 28, 2023
• Study Completion: August 31, 2023
• Last Updated: June 8, 2025

Record last verified: 2023-09

Locations

IE (1); DE (1)