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 (NOVOGLUCOSE)

Double-blind, Placebo-controlled, Randomized Pilot 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

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 Overview

• Status: Completed
• Conditions: Prediabetic State; Dysglycemia
• Intervention / Treatment: Dietary supplement: NZ-GHMH-01; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75012
    • Clinical Investigation Unit Paris
  • Pays De La Loire
    • Saint-Herblain, Pays De La Loire, France, 44800
      • Clinical Investigation Unit Biofortis
• Romania
  • Braşov, Romania
    • Neomed Brasov
  • Bucuresti, Romania, 030167
    • Fundatia Ana Aslan International
  • Bucuresti, Romania
    • Military Hospital- Spitalul Militar Central Dr "Carol Davila"
  • Bucuresti, Romania
    • Parhon Institute- Institutul National de Endocrinologie C.I. Parhon
  • Suceava, Romania, 720224
    • Suceava County Hospital - Spitalul Județean de Urgență "Sfântul Ioan cel Nou"
• United Kingdom
  • Glasgow, United Kingdom, G20 0XA
    • CPS Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NZ-GHMH-01; Dietary supplement in shape of capsule to be taken once per day in the evening.	Dietary supplement: NZ-GHMH-01; Each randomized subject will consume 1 capsule daily bringing 100 mg (≥ 2 x 109 CFU) of active ingredient during 16 weeks (from V2 to V5 visits).
Placebo Comparator: Placebo; The placebo is in shape of capsule to be taken once per day in the evening and in which only the active ingredients are not present.	Dietary supplement: Placebo; Each randomized subject will consume 1 capsule with no active ingredient daily during 16 weeks (from V2 to V5 visits).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycated Hemoglobin A1c (HbA1c)	Change from Baseline of HbA1c level between V2 and V5 visits (in %) between both groups.	V2 (randomization) and V5 (16 weeks of intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycated Hemoglobin A1c (HbA1c)	Change from baseline of HbA1c level	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)	V2 (randomization) and V5 (16 weeks of intervention)
Glucose kinetic parameters: T max	Change from baseline of T max (min)	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)	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)	V2 (randomization) and V5 (16 weeks of intervention)
Homeostasis Model of Assessment - insulin resistance (HOMA-IR)	Change from baseline of HOMA-IR index	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	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	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	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	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	V2 (randomization) and V5 (16 weeks of intervention)
Glucagon Like Peptide 1 (GLP-1)	Change from baseline of GLP-1 level	V2 (randomization) and V5 (16 weeks of intervention)
Weight	Change from baseline of weight(in kg)	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)	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)	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	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)	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)	V1 (screening) and V5 (16 weeks of intervention)
Triglycerides	fasting blood concentrations of triglycerides (expressed in g/L)	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)	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	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)	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	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)	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	V2 (randomization) and V5 (16 weeks of intervention)
Gastrointestinal Symptoms	Change from baseline of gastrointestinal symptoms (evaluated with Gastrointestinal Symptom Rating Scale)	V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverses events	Incidence of adverses events	V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
Heart Rate	overall health through hemodynamic parameters: Heart Rate (expressed in bpm)	V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
Blood pressure	overall health through hemodynamic parameters: Systolic Blood Pressure and Diastolic Blood Pressure (expressed in mmHg)	V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
Complete Blood Count (CBC)	overall health through CBC: Leukocytes, Red blood cells, Hemoglobin, Hematocrit, Poly. Neutrophils, Poly. Neutrophils, Poly. Eosinophils, Poly. Eosinophils, Poly. Basophils, Poly. Basophils, Lymphocytes, Lymphocytes, Monocytes, Monocytes, Platelets (expressed in Giga/L and %)	V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
Fecal zonulin	Change from baseline of fecal zonulin level	V2 (randomization) and V5 (16 weeks of intervention)
Fecal calprotectin	Change from baseline of fecal calprotectin level	V2 (randomization) and V5 (16 weeks of intervention)

Collaborators and Investigators

• Sponsor: Novozymes A/S
• Collaborators: Biofortis, Merieux NutriSciences

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): November 29, 2022
• Study Completion (Actual): November 29, 2022

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State
• Other Study ID Numbers: PEC20022; 2021-A00210-41 (Other Identifier: ID-RCB Number); 295204 (Other Identifier: IRAS Project ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No