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

Prediabetic State Clinical Trial

— NOVOGLUCOSE  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04767789
• Other study ID #: PEC20022
• Secondary ID: 2021-A00210-4129
• Status: Completed
• Phase: N/A
• Start date: May 12, 2021
• Est. completion date: November 29, 2022

Study information

• Verified date: June 2023
• Source: Novozymes A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: November 29, 2022
• Est. primary completion date: November 29, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Dysglycemia
• Prediabetic State

Intervention

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

Locations

Country	Name	City	State
France	Clinical Investigation Unit Paris	Paris
France	Clinical Investigation Unit Biofortis	Saint-Herblain	Pays De La Loire
Romania	Neomed Brasov	Brasov
Romania	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	Bucuresti
Romania	Suceava County Hospital - Spitalul Jude?ean de Urgen?a "Sfântul Ioan cel Nou"	Suceava
United Kingdom	CPS Research	Glasgow

Sponsors (2)

Lead Sponsor	Collaborator
Novozymes A/S	Biofortis, Merieux NutriSciences

Countries where clinical trial is conducted

France,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Other	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)
Other	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)
Other	Fecal zonulin	Change from baseline of fecal zonulin level	V2 (randomization) and V5 (16 weeks of intervention)
Other	Fecal calprotectin	Change from baseline of fecal calprotectin level	V2 (randomization) and V5 (16 weeks of intervention)
Primary	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	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)
Secondary	Glucose kinetic parameters: ?Peak and Cmax	Change from baseline of ?Peak (g/L) and Cmax (g/L)	V2 (randomization) and V5 (16 weeks of intervention)
Secondary	Glucose kinetic parameters: T max	Change from baseline of T max (min)	V2 (randomization) and V5 (16 weeks of intervention)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Glycemia	Change from baseline of glycemia level	V2 (randomization) and V5 (16 weeks of intervention)
Secondary	Glucagon Like Peptide 1 (GLP-1)	Change from baseline of GLP-1 level	V2 (randomization) and V5 (16 weeks of intervention)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Total bilirubin	Change from baseline of Total bilirubin levels (expressed in umol/L)	V1 (screening) and V5 (16 weeks of intervention)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Tumor Necrosis Factors alpha (TNFa)	Change from baseline of the TNFa	V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
Secondary	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)
Secondary	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)
Secondary	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)