Efficacy and Safety of 12-weeks Supplementation of Eubacterium Hallii on Insulin Sensitivity and Glycaemic Control

• ClinicalTrials.gov Identifier: NCT04529473
• Recruitment Status: Recruiting
• First Posted: August 27, 2020
• Last Update Posted: January 20, 2022
• Sponsor: Atlantia Food Clinical Trials
• Collaborator: Caelus Pharmaceuticals BV
• Information provided by (Responsible Party): Atlantia Food Clinical Trials

Study Description

Brief Summary:

This 12 week placebo-controlled study evaluates the efficacy and safety of E. hallii supplementation.

Condition or disease	Intervention/treatment	Phase
Pre Diabetes; Impaired Glucose Tolerance; Insulin Sensitivity; Insulin Resistance; Glucose Metabolism Disorders; Metabolic Syndrome	Dietary Supplement: Eubacterium hallii; Other: Placebo	Not Applicable

Detailed Description:

There is an increased awareness that the bacteria which forms our microbiome, plays a crucial role in human health and diseases. Numerous studies have highlighted the therapeutic potential of specific bacteria in preventing and treating metabolic, gastrointestinal and other diseases.

The aim of the study is evaluate the effect of administration of a next generation probiotic, Eubacterium hallii, versus placebo on insulin sensitivity and glycemic control, in volunteers with some markers of metabolic syndrome.

Participants will receive their randomized study product daily for 12 weeks. The target population will be otherwise healthy hyperglycaemic adults.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Double-blind, Randomized, Placebo-controlled Trial to Assess the Efficacy and Safety of 12-weeks Supplementation of Eubacterium Hallii on Insulin Sensitivity and Markers of Glycaemic Control in Healthy Hyperglycaemic Adults
• Actual Study Start Date: February 3, 2021
• Estimated Primary Completion Date: April 1, 2022
• Estimated Study Completion Date: April 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; 1 capsule per day, consumed orally, before breakfast for the duration of the study.	Other: Placebo; Placebo capsules are identical to the active treatment
Experimental: Eubacterium hallii; 1 capsule per day, consumed orally, before breakfast for the duration of the study.	Dietary Supplement: Eubacterium hallii; Eubacterium hallii, ≥ 1x10^9 live bacterial cells (per capsule)

Outcome Measures

Primary Outcome Measures :

1. 2-hour blood glucose incremental Area Under the Curve (AUC) [ Time Frame: From Baseline to Week 12 ]
   as measured by standard Oral Glucose Tolerance Test (OGTT)
2. 2-hour blood insulin incremental AUC [ Time Frame: From Baseline to Week 12 ]
   as measured by standard OGTT
3. Post-prandial insulin sensitivity [ Time Frame: From Baseline to Week 12 ]
   as measured by insulin sensitivity index-OGTT (ISI-OGTT)
4. Glycated haemoglobin (HbA1c) [ Time Frame: From Baseline to Week 12 ]
   Change from baseline to Week 12 in each of the treatment groups as compared to placebo in A1c levels

Secondary Outcome Measures :

1. Glycaemic Variability (GV) over the 24-hr period [ Time Frame: From Baseline to Week 12 ]
   as measured by the Professional Continuous Glucose Monitoring (PCGM) device over 10as measured by the PCGM device over 10-14 days at the start and end of intervention
2. Glycaemic Control (GC) over the 24-hr period [ Time Frame: From Baseline to Week 12 ]
   as measured by the PCGM device over 10-14 days at the start and end of intervention
3. GV during sleeping hours [ Time Frame: From Baseline to Week 12 ]
   as measured by the PCGM device over 10-14 days at the start and end of intervention
4. Fasting Blood Glucose [ Time Frame: From Baseline to Week 12 ]
   Change from baseline to Week 12 in each of the treatment groups as compared to placebo in fasting blood glucose levels
5. Blood Pressure [ Time Frame: From Baseline to Week 12 ]
   Change from baseline to Week 12 in Systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg)

Other Outcome Measures:

1. Safety Blood Profile [ Time Frame: From Baseline to Week 12 ]
   Change from baseline to Week 12 in the incidence of abnormal laboratory test results
2. Vitals [ Time Frame: From Baseline to Week 12 ]
   Change from baseline to Week 12 in Heart Rate
3. Vitals [ Time Frame: From Baseline to Week 12 ]
   Change from baseline to Week 12 in Temperature
4. Adverse Events (AE) [ Time Frame: From Baseline to Week 12 ]
   Change from baseline to Week 12 in AEs

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 69 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Give written informed consent;
• Be male and aged between 21 and 69 years, inclusive; or be female and aged between 45 and 69, inclusive
• Have a body mass index between 18.5 to 43 Kg/m2;
• Have a waist-circumference > 94cm (37inches) for males and ≥80cm (31.5inches) for females (IDF criterion for Metabolic Syndrome);
• Have a measured Hb1Ac level of 5.5 to 8.0% (36.6 to 63.9 mmol/mol, 6.2 to 10 mmol/L) inclusive;
• If participant has a prior diagnosis of pre-diabetes or Type II diabetes who has been unmedicated for 3-months prior to screening;
• Be female and be post or peri-menopausal (female who have not had a menstrual period within the previous 9 months)
• Be willing to maintain dietary habits and physical activity levels throughout the study period;
• Be willing to consume the investigational product daily for the duration of the study;
• Capable and willing to wear the PCGM sensor
• 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

Exclusion Criteria:

• Morbid obesity (BMI ≥43.1);
• Prior diagnosis of Type I diabetes mellitus (i.e. a clinical diagnosis made before the screening visit of this study);
• Participants with a prior diagnosis of Type II diabetes who have received a glucose lowering medication (e.g. Metformin, Sulfonylureas, Meglitinides, Thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors) or insulin therapy, in the previous 3 months;
• Presence of significant dyslipidaemia (Note: ongoing treatment with stable (3-months) low-dose statins is acceptable);
• Presence of significant cardiovascular disease, including but not limited to significant systemic hypertension (SBP ≥160 mmHg and/or DBP ≥100 mmHg), pulmonary hypertension, or other unstable cardiopulmonary conditions, limiting or unstable angina, congestive heart failure. (Note: ongoing treatment with stable (3 months) antihypertensives is acceptable);
• Present or recent (within 2 months of screening) use of dietary supplements intended to affect the level of blood glucose. The use of replacement doses of Vitamin D, calcium supplements, and a single daily multi-vitamin tablet is allowed, if stable (3-months);
• Participant regularly takes probiotic supplements, or has done within the 4-weeks prior to screening or plans to during the study;
• Participant has taken oral antibiotics, antifungal, antiparasitic, or antiviral treatment in the 4-weeks prior to screening (topical permissible);
• Participant has a history of co-existing gastrointestinal, and/or gynaecological, and/or urologic pathology (e.g. colon cancer, colitis, Crohn's Disease, Celiac, Endometriosis, prostate cancer);
• 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);
• Presence or history of significant other acute or chronic coexisting illness which, in the opinion of the investigator, could compound the outcome of the study, including but not limited to kidney, liver or renal disease/dysfunction, uncontrolled metabolic disease, atrial fibrillation, syncope and known or suspected right-to-left, bi-directional or transient right-to-left cardiac shunts;
• Participant has a cardiac pacemaker;
• 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 extreme dietary practices or exercise;
• Having lost >5% of their body weight within 3-months prior to screening;
• Participant has a history of drug and/or alcohol abuse at the time of enrolment;
• Participation in a clinical trial with an investigational product within 60 days before screening, or plans to participate in another study during the study period;
• Participant has a history of non-compliance with medical treatments
• Female subjects with a premature onset of menopause ( those aged less than 45 years at onset) or those whose menopause has been brought on early either by intended or unintended pharmacological intervention (resulting from the treatment of other conditions)

Contacts and Locations

Contacts

Contact: Andrea Doolan; +353 21 430 7442; adoolan@atlantiatrials.com

Contact: Luc Sterkman, MD; l.sterkman@caelushealth.com

Locations

United States, Illinois

Atlantia Food Clinical Trials, Chicago; Recruiting

Chicago, Illinois, United States, 60611

Contact: Kevin O'Regan 312-535-9440 koregan@atlantiatrials.com

Principal Investigator: Elizabeth Lowden

Ireland

Atlantia Food Clinical Trials; Recruiting

Cork, Ireland, T23 R50R

Contact: Andrea Doolan +353 21 430 7442 adoolan@atlantiatrials.com

United Kingdom

CPS Research; Recruiting

Glasgow, Scotland, United Kingdom, G20 0XA

Contact: Gordan Crawford +44 (0)141 946 7888 gordon.crawford@cpsresearch.co.uk

Principal Investigator: Jennifer Elliot

Sponsors and Collaborators

Atlantia Food Clinical Trials

Caelus Pharmaceuticals BV

Investigators

• Principal Investigator: James Ryan, MD; Atlantia Food Clinical Trials

More Information

• Responsible Party: Atlantia Food Clinical Trials
• ClinicalTrials.gov Identifier: NCT04529473
• Other Study ID Numbers: AFCRO-115
• First Posted: August 27, 2020
• Last Update Posted: January 20, 2022
• Last Verified: January 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Metabolic Syndrome; Insulin Resistance; Prediabetic State; Glucose Intolerance; Metabolic Diseases; Glucose Metabolism Disorders; Hypersensitivity; Hyperinsulinism; Immune System Diseases; Diabetes Mellitus; Endocrine System Diseases; Hyperglycemia