Clinical trial 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetic State
Dysglycemia
Lead sponsor: Novozymes A/S
Sponsor class: INDUSTRY
Collaborators: name: Biofortis, Merieux NutriSciences
First posted: 2021-02-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Glycated Hemoglobin A1c (HbA1c)
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
Secondary outcomes:
measure: Glycated Hemoglobin A1c (HbA1c)
timeFrame: V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Glucose kinetic parameters: ΔPeak and Cmax
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Glucose kinetic parameters: T max
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Incremental Area Under the Curve (iAUC) of glucose
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Incremental Area Under the Curve (iAUC) of insulinemia
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Homeostasis Model of Assessment - insulin resistance (HOMA-IR)
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Quantitative Insulin sensitivity Check Index (QUICKI)
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Insulin Sensitivity Index (ISI)
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Fasting Plasma Glucose (FPG)
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Fasting insulinemia
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Glycemia
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Glucagon Like Peptide 1 (GLP-1)
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Weight
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Body Mass Index (BMI)
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Waist and Hip
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Anthropometric ratios
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Liver function
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Total bilirubin
timeFrame: V1 (screening) and V5 (16 weeks of intervention)
measure: Triglycerides
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Lipid homeostasis
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: high-sensitivity C-reactive Protein (CRPhs)
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Cytokines
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Tumor Necrosis Factors alpha (TNFα)
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Overall health
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Blood metabolites
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Gastrointestinal Symptoms
timeFrame: V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
Other outcomes:
measure: Incidence of adverses events
timeFrame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Heart Rate
timeFrame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Blood pressure
timeFrame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Complete Blood Count (CBC)
timeFrame: V1 (Inclusion), V2 (randomization), V3 (4 weeks of intervention), V4 (12 weeks of intervention) and V5 (16 weeks of intervention)
measure: Fecal zonulin
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
measure: Fecal calprotectin
timeFrame: V2 (randomization) and V5 (16 weeks of intervention)
Locations:
city: Saint-Herblain
country: France
facility: Clinical Investigation Unit Biofortis
state: Pays De La Loire
city: Paris
country: France
facility: Clinical Investigation Unit Paris
city: Braşov
country: Romania
facility: Neomed Brasov
city: Bucuresti
country: Romania
facility: Fundatia Ana Aslan International
city: Bucuresti
country: Romania
facility: Military Hospital- Spitalul Militar Central Dr "Carol Davila"
city: Bucuresti
country: Romania
facility: Parhon Institute- Institutul National de Endocrinologie C.I. Parhon
city: Suceava
country: Romania
facility: Suceava County Hospital - Spitalul Județean de Urgență "Sfântul Ioan cel Nou"
city: Glasgow
country: United Kingdom
facility: CPS Research
Study officials:
References: