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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

Not Applicable
Completed
Conditions
Prediabetic State
Dysglycemia
Interventions
Dietary Supplement: NZ-GHMH-01
Dietary Supplement: Placebo
Registration Number
NCT04767789
Lead Sponsor
Novozymes A/S
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NZ-GHMH-01NZ-GHMH-01Dietary supplement in shape of capsule to be taken once per day in the evening.
PlaceboPlaceboThe 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.
Primary Outcome Measures
NameTimeMethod
Glycated Hemoglobin A1c (HbA1c)V2 (randomization) and V5 (16 weeks of intervention)

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

Secondary Outcome Measures
NameTimeMethod
Glucose kinetic parameters: ΔPeak and CmaxV2 (randomization) and V5 (16 weeks of intervention)

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

Glucose kinetic parameters: T maxV2 (randomization) and V5 (16 weeks of intervention)

Change from baseline of T max (min)

Incremental Area Under the Curve (iAUC) of glucoseV2 (randomization) and V5 (16 weeks of intervention)

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

Incremental Area Under the Curve (iAUC) of insulinemiaV2 (randomization) and V5 (16 weeks of intervention)

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

Homeostasis Model of Assessment - insulin resistance (HOMA-IR)V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of HOMA-IR index

Glycated Hemoglobin A1c (HbA1c)V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of HbA1c level

Quantitative Insulin sensitivity Check Index (QUICKI)V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of QUICKI index

GlycemiaV2 (randomization) and V5 (16 weeks of intervention)

Change from baseline of glycemia level

Insulin Sensitivity Index (ISI)V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of ISI index

Fasting Plasma Glucose (FPG)V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of FPG levels

Fasting insulinemiaV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of fasting insulinemia levels

Glucagon Like Peptide 1 (GLP-1)V2 (randomization) and V5 (16 weeks of intervention)

Change from baseline of GLP-1 level

WeightV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of weight(in kg)

Body Mass Index (BMI)V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of BMI (in kg/m2)

Waist and HipV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

Liver functionV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

Total bilirubinV1 (screening) and V5 (16 weeks of intervention)

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

TriglyceridesV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

Anthropometric ratiosV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

Lipid homeostasisV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

CytokinesV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

Tumor Necrosis Factors alpha (TNFα)V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of the TNFα

Blood metabolitesV2 (randomization) and V5 (16 weeks of intervention)

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

high-sensitivity C-reactive Protein (CRPhs)V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

Change from baseline of the CRPhs

Overall healthV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

Gastrointestinal SymptomsV2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

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

Trial Locations

Locations (8)

Neomed Brasov

🇷🇴

Braşov, Romania

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

🇷🇴

Bucuresti, Romania

Clinical Investigation Unit Paris

🇫🇷

Paris, France

Clinical Investigation Unit Biofortis

🇫🇷

Saint-Herblain, Pays De La Loire, France

Fundatia Ana Aslan International

🇷🇴

Bucuresti, Romania

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

🇷🇴

Suceava, Romania

Military Hospital- Spitalul Militar Central Dr "Carol Davila"

🇷🇴

Bucuresti, Romania

CPS Research

🇬🇧

Glasgow, United Kingdom

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