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
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Paris, France, 75012
- Clinical Investigation Unit Paris
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Pays De La Loire
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Saint-Herblain, Pays De La Loire, France, 44800
- Clinical Investigation Unit Biofortis
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Braşov, Romania
- Neomed Brasov
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Bucuresti, Romania, 030167
- Fundatia Ana Aslan International
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Bucuresti, Romania
- Military Hospital- Spitalul Militar Central Dr "Carol Davila"
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Bucuresti, Romania
- Parhon Institute- Institutul National de Endocrinologie C.I. Parhon
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Suceava, Romania, 720224
- Suceava County Hospital - Spitalul Județean de Urgență "Sfântul Ioan cel Nou"
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Glasgow, United Kingdom, G20 0XA
- CPS Research
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
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Experimental: NZ-GHMH-01
Dietary supplement in shape of capsule to be taken once per day in the evening.
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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).
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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.
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Each randomized subject will consume 1 capsule with no active ingredient daily during 16 weeks (from V2 to V5 visits).
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Glycated Hemoglobin A1c (HbA1c)
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from Baseline of HbA1c level between V2 and V5 visits (in %) between both groups.
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V2 (randomization) and V5 (16 weeks of intervention)
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Glycated Hemoglobin A1c (HbA1c)
Time Frame: V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of HbA1c level
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V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Glucose kinetic parameters: ΔPeak and Cmax
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of ΔPeak (g/L) and Cmax (g/L)
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V2 (randomization) and V5 (16 weeks of intervention)
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Glucose kinetic parameters: T max
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of T max (min)
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V2 (randomization) and V5 (16 weeks of intervention)
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Incremental Area Under the Curve (iAUC) of glucose
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of the value of the iAUC of glucose, obtained during OGTT (iAUC0-120min)
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V2 (randomization) and V5 (16 weeks of intervention)
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Incremental Area Under the Curve (iAUC) of insulinemia
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of the value of the iAUC of insulinemia, obtained during OGTT (iAUC0-120min)
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V2 (randomization) and V5 (16 weeks of intervention)
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Homeostasis Model of Assessment - insulin resistance (HOMA-IR)
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of HOMA-IR index
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Quantitative Insulin sensitivity Check Index (QUICKI)
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of QUICKI index
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Insulin Sensitivity Index (ISI)
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of ISI index
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Fasting Plasma Glucose (FPG)
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of FPG levels
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Fasting insulinemia
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of fasting insulinemia levels
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Glycemia
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of glycemia level
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V2 (randomization) and V5 (16 weeks of intervention)
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Glucagon Like Peptide 1 (GLP-1)
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of GLP-1 level
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V2 (randomization) and V5 (16 weeks of intervention)
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Weight
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of weight(in kg)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Body Mass Index (BMI)
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of BMI (in kg/m2)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Waist and Hip
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of Waist measurement (in cm) and Hip Circumference (in cm)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Anthropometric ratios
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of Waist to Hip ratio and Waist to Height ratio
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Liver function
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of Aspartate Amino Transferase (ASAT), Alanine Amino Transferase (ALAT) and Gamma Glutamyl Transpeptidase (GGT) levels (expressed in ukat/L)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Total bilirubin
Time Frame: V1 (screening) and V5 (16 weeks of intervention)
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Change from baseline of Total bilirubin levels (expressed in umol/L)
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V1 (screening) and V5 (16 weeks of intervention)
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Triglycerides
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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fasting blood concentrations of triglycerides (expressed in g/L)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Lipid homeostasis
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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fasting blood concentrations of total cholesterol, High Density Lipoprotein cholesterol (HDLc), non-HDLc and Low Density Lipoprotein cholesterol (LDLc) (expressed in mmol/L)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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high-sensitivity C-reactive Protein (CRPhs)
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of the CRPhs
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Cytokines
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of the Cytokines IL-1alpha, IL-1beta, IL-6, IL-10, IL-12p70 and monocyte chemoattractant protein 1 (MCP1)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Tumor Necrosis Factors alpha (TNFα)
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of the TNFα
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Overall health
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of participant overall health (evaluated with SF36 questionnaire)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Blood metabolites
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of Cholic acid, Chenodeoxycholic acid, Deoxycholic acid, Lithocholic acid, Ursodeoxy cholic acid, Taurocholic acid and Glycochenodeoxycholic acids
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V2 (randomization) and V5 (16 weeks of intervention)
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Gastrointestinal Symptoms
Time Frame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Change from baseline of gastrointestinal symptoms (evaluated with Gastrointestinal Symptom Rating Scale)
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V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Other Outcome Measures
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Incidence of adverses events
Time Frame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Incidence of adverses events
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V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Heart Rate
Time Frame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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overall health through hemodynamic parameters: Heart Rate (expressed in bpm)
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V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Blood pressure
Time Frame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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overall health through hemodynamic parameters: Systolic Blood Pressure and Diastolic Blood Pressure (expressed in mmHg)
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V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Complete Blood Count (CBC)
Time Frame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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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 %)
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V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
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Fecal zonulin
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of fecal zonulin level
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V2 (randomization) and V5 (16 weeks of intervention)
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Fecal calprotectin
Time Frame: V2 (randomization) and V5 (16 weeks of intervention)
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Change from baseline of fecal calprotectin level
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V2 (randomization) and V5 (16 weeks of intervention)
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
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)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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