Clinical Trial to Evaluate the Efficacy and Safety of the Probiotic Strains Limosilactocillus Reuteri DSM 32910 and Lacticaseibacillus Paracasei DSM 32851 on Glucose Homeostatis in Prediabetic Adults

Novozymes A/S100 enrolled

Overview

The aim of this international, randomized, parallel arms, double-blind, placebo-controlled clinical trial is to investigate the safety and efficacy of a combination of the two Lactobacillus strains (NZ-GHMH-01) on glucose and insulin metabolism, in prediabetic subjects. This trial will include prediabetic (insulin resistant) subjects with excessive body weight (over-weight or obese, showing abdominal or visceral obesity) to be able to investigate the effect of the probiotic NZ-GHMH-01 on glycaemic control.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

100

Conditions

Prediabetic State Dysglycemia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Aged between 18 and 75 years (limits included) * Having BMI between 18,5 and 40 kg/m² (limits included) * Prediabetic * For women: Non menopausal with the same reliable contraception or menopausal without or with hormone replacement therapy * Agreeing to keep his lifestyle habits unchanged throughout the study * With stable weight within ± 5% in the last three months * Having a good general and mental health with in the opinion of the investigator * Having signed informed consent form * Affiliated with a social security scheme (for French sites only) * Agreed to be registered on the subjects in the "VRB" (biomedical research file (for French sites only)) * Having HbA1c level ≥ 5.7% and ≤ 6.4% Exclusion Criteria: * Metabolic disorder such as diabetes or uncontrolled thyroidal trouble or other metabolic disorder; * Having a history of medication for diabetes and dyslipidemia * Uncontrolled hypertension * Severe chronic disease or gastrointestinal disorders * Having done the second injection of COVID-19 vaccination or between the first and the second injection within the last 2 weeks prior to V1 visit * Food allergy or intolerance or hypersensitivity to any of the study products' ingredient * Pregnant or lactating women or intending to become pregnant within 3 months ahead * Smoking subject (more than 5 cigarettes per day) * Having a history of bariatric surgery * Having a history of any surgery in the 3 months before V1 visit or having scheduled any surgery within 6 months ahead * Under dietary supplement except fibers, omega 3 and vitamins (other than Vitamin D3) if the subject agrees to keep his/her intake unchanged throughout the study; * Under treatment which could significantly affect parameter(s) followed during the study * Under antibiotic treatment in the 3 to 6 months before V1 visit * With significant change in food habits or in physical activity in the 3 months before V1 visit or not agreeing to keep them unchanged throughout the study * With a current or planned in the next 5 months specific diet (hyper or hypocaloric, vegan…) or putted in place since less than 3 months before the inclusion visit * With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator * Abuse of alcohol, defined as more than 21 alcohol units per week for men and 14 units for women, or unwillingness to refrain from alcohol intake the day before V2 and V5 visits * Having a lifestyle deemed incompatible with the study according to the investigator * Taking part in another clinical trial or having taken part in another clinical trial in the 3 months before the inclusion visit; * Having received, during the last 12 months, indemnities for clinical trial higher or equal to 4500 Euros (for French sites only); * Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision; * Presenting a psychological or linguistic incapability to sign the informed consent; * Impossible to contact in case of emergency. * Having blood ASAT, ALAT or GGT levels out of range and clinically significant according to the investigator * Having CBC with hemoglobin \< 11 g/L or leucocytes \< 3000 /mm3 or leucocytes \> 16000 /mm3 or clinically significant abnormality according to the investigator

Locations (8)

Clinical Investigation Unit Biofortis

Saint-Herblain, Pays de la Loire Region, France

Clinical Investigation Unit Paris

Paris, France

Neomed Brasov

Brasov, Romania

Fundatia Ana Aslan International

Bucharest, Romania

Military Hospital- Spitalul Militar Central Dr "Carol Davila"

Bucharest, Romania

Parhon Institute- Institutul National de Endocrinologie C.I. Parhon

Bucharest, Romania

Suceava County Hospital - Spitalul Județean de Urgență "Sfântul Ioan cel Nou"

Suceava, Romania

CPS Research

Glasgow, United Kingdom

Outcomes

Primary Outcomes

Glycated Hemoglobin A1c (HbA1c)

Change from Baseline of HbA1c level between V2 and V5 visits (in %) between both groups.

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Secondary Outcomes

Glycated Hemoglobin A1c (HbA1c)

Change from baseline of HbA1c level

Time frame: V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Glucose kinetic parameters: ΔPeak and Cmax

Change from baseline of ΔPeak (g/L) and Cmax (g/L)

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Glucose kinetic parameters: T max

Change from baseline of T max (min)

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Incremental Area Under the Curve (iAUC) of glucose

Change from baseline of the value of the iAUC of glucose, obtained during OGTT (iAUC0-120min)

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Incremental Area Under the Curve (iAUC) of insulinemia

Change from baseline of the value of the iAUC of insulinemia, obtained during OGTT (iAUC0-120min)

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Homeostasis Model of Assessment - insulin resistance (HOMA-IR)

Change from baseline of HOMA-IR index

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Quantitative Insulin sensitivity Check Index (QUICKI)

Change from baseline of QUICKI index

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Insulin Sensitivity Index (ISI)

Change from baseline of ISI index

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Fasting Plasma Glucose (FPG)

Change from baseline of FPG levels

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Fasting insulinemia

Change from baseline of fasting insulinemia levels

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Glycemia

Change from baseline of glycemia level

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Glucagon Like Peptide 1 (GLP-1)

Change from baseline of GLP-1 level

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Weight

Change from baseline of weight(in kg)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Body Mass Index (BMI)

Change from baseline of BMI (in kg/m2)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Waist and Hip

Change from baseline of Waist measurement (in cm) and Hip Circumference (in cm)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Anthropometric ratios

Change from baseline of Waist to Hip ratio and Waist to Height ratio

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Liver function

Change from baseline of Aspartate Amino Transferase (ASAT), Alanine Amino Transferase (ALAT) and Gamma Glutamyl Transpeptidase (GGT) levels (expressed in ukat/L)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Total bilirubin

Change from baseline of Total bilirubin levels (expressed in umol/L)

Time frame: V1 (screening) and V5 (16 weeks of intervention)

Triglycerides

fasting blood concentrations of triglycerides (expressed in g/L)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Lipid homeostasis

fasting blood concentrations of total cholesterol, High Density Lipoprotein cholesterol (HDLc), non-HDLc and Low Density Lipoprotein cholesterol (LDLc) (expressed in mmol/L)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

high-sensitivity C-reactive Protein (CRPhs)

Change from baseline of the CRPhs

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Cytokines

Change from baseline of the Cytokines IL-1alpha, IL-1beta, IL-6, IL-10, IL-12p70 and monocyte chemoattractant protein 1 (MCP1)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Tumor Necrosis Factors alpha (TNFα)

Change from baseline of the TNFα

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Overall health

Change from baseline of participant overall health (evaluated with SF36 questionnaire)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Blood metabolites

Change from baseline of Cholic acid, Chenodeoxycholic acid, Deoxycholic acid, Lithocholic acid, Ursodeoxy cholic acid, Taurocholic acid and Glycochenodeoxycholic acids

Time frame: V2 (randomization) and V5 (16 weeks of intervention)

Gastrointestinal Symptoms

Change from baseline of gastrointestinal symptoms (evaluated with Gastrointestinal Symptom Rating Scale)

Time frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)