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Completed

NCT Number: NCT04767789

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.

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Clinical Investigation Unit Biofortis, Saint-Herblain, Pays de la Loire Region, France

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

NZ-GHMH-01

Dietary Supplement

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

Dietary Supplement

Each randomized subject will consume 1 capsule with no active ingredient daily during 16 weeks (from V2 to V5 visits).

Primary outcomes

  1. Glycated Hemoglobin A1c (HbA1c)

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

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

Secondary outcomes

  1. Glycated Hemoglobin A1c (HbA1c)

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

    Change from baseline of HbA1c level

  2. Glucose kinetic parameters: ΔPeak and Cmax

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

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

  3. Glucose kinetic parameters: T max

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

    Change from baseline of T max (min)

  4. Incremental Area Under the Curve (iAUC) of glucose

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

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

  5. Incremental Area Under the Curve (iAUC) of insulinemia

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

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

  6. 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)

    Change from baseline of HOMA-IR index

  7. 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)

    Change from baseline of QUICKI index

  8. Insulin Sensitivity Index (ISI)

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

    Change from baseline of ISI index

  9. Fasting Plasma Glucose (FPG)

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

    Change from baseline of FPG levels

  10. Fasting insulinemia

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

    Change from baseline of fasting insulinemia levels

  11. Glycemia

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

    Change from baseline of glycemia level

  12. Glucagon Like Peptide 1 (GLP-1)

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

    Change from baseline of GLP-1 level

  13. Weight

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

    Change from baseline of weight(in kg)

  14. Body Mass Index (BMI)

    Time frame: 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)

  15. Waist and Hip

    Time frame: V2 (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)

  16. Anthropometric ratios

    Time frame: V2 (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

  17. Liver function

    Time frame: V2 (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)

  18. Total bilirubin

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

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

  19. Triglycerides

    Time frame: V2 (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)

  20. Lipid homeostasis

    Time frame: V2 (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)

  21. 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)

    Change from baseline of the CRPhs

  22. Cytokines

    Time frame: V2 (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)

  23. 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)

    Change from baseline of the TNFα

  24. Overall health

    Time frame: V2 (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)

  25. Blood metabolites

    Time frame: V2 (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

  26. Gastrointestinal Symptoms

    Time frame: V2 (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)

Other outcomes

  1. 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)

    Incidence of adverses events

  2. Heart Rate

    Time frame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

    overall health through hemodynamic parameters: Heart Rate (expressed in bpm)

  3. Blood pressure

    Time frame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)

    overall health through hemodynamic parameters: Systolic Blood Pressure and Diastolic Blood Pressure (expressed in mmHg)

  4. 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)

    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 %)

  5. Fecal zonulin

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

    Change from baseline of fecal zonulin level

  6. Fecal calprotectin

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

    Change from baseline of fecal calprotectin level

Sponsors and collaborators

Lead sponsor

Novozymes A/S

Industry

Collaborators

  • Biofortis, Merieux NutriSciences

Registry information

Official study title

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

Acronym: NOVOGLUCOSE

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Feb 23, 2021
Registry last updated
Jun 15, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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