Clinical trial NCT04753580: Sampling of Human Microbiota in Order to Test, on a Mouse Model, Individualized Intervention Strategies During Aging
Official title: Sampling of Human Microbiota in Order to Test, on a Mouse Model, Individualized Intervention Strategies During Aging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Frail Volunteers
Keywords: Genetic
Elderly
Microbiota
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Unite de Nutrition Humaine UMR 1019- INRAE
name: Unite MetaGenoPolis INRAE
name: France MICALIS Equipe ProbiHote UMR INRAE
First posted: 2021-02-15
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Human microbial flora transfer studies in rodent models have clearly identified that age-associated microbiota dysbiosis can play a decisive role with respect to pathologies or complications linked to aging: increased intestinal permeability, in place of systemic inflammation, dysfunction of immune cells and insulin resistance.

This trial therefore aims to validate the process of ex vivo transfer to the rat of human microbiota selected from three categories of male individuals: young adults, healthy older adults and frail older adults, with the evaluation of the bacterial population of stool by analysis of the 16S rRNA gene.

Detailed description: This is a pilot study to validate a process of ex vivo stool transfer from humans to rats. Single-center intervention research with minimal risks and constraints.

Exploration of the bacterial composition of the intestinal microbiota in healthy adult volunteers, healthy elderly and frail elderly. The evaluation of the bacterial population of the stool will be done by analysis of the 16S rRNA gene.

The secondary objectives will evaluate the muscular functional abilities the body composition measurement, at Day 0 (visit 2) and the inflammatory status at Day -7 (visit 1).

Seconds parameters are the following :

seated, standing, walking, and direction changes, a balance test, a walking speed test and a chair lift test, the maximum voluntary force of manual gripping, the maximum muscle strength of the quadriceps and the level of autonomy

This protocol includes 3 visits :

* Visit 1 : Day -7 (allowed until Day-14) = inclusion
* Visit 2 : Day 0 = tests and questionnaires
* Visit 3 : Day +7 (allowed from Day+1) = stool collect

Eligibility criteria: Inclusion Criteria:

* Volunteer over the age 18,
* More than 50 kg and having a Body Mass Index (BMI) between 18 and 30 kg / m2 (inclusive),
* Subject aged between 20 and 35 years inclusive ("healthy adult" group, or 65 years (inclusive) and over ("healthy elderly" and "frail elderly" groups),
* Score of the Short Emergency Geriatric Assesment grid (SEGA - A) strictly less than 8 (see appendix 1) ("healthy adult" and "healthy elderly" groups), or greater than or equal to 8 ("frail elderly" group),
* Subject capable of giving informed consent to participate in the research,
* Subject having an affiliation to the French Social Security system.

Exclusion Criteria:

Healthy adult group and Healthy elderly group:

* Subject presenting an acute pathology (unstable pathology), a life expectancy of \<3 months or major neuro-cognitive disorders,
* treated with antibiotic therapy 3 months before the start of the protocol,
* in the impossibility of carrying out the planned functionality tests,
* carrier of Pacemaker or implantable defibrillator,
* with renal insufficiency (clearance \<50 ml / min according to the CKD-EPI formula),
* presenting an untreated metabolic syndrome (presenting 3 of the 5 following criteria: waist circumference greater than 94 cm, blood triglyceride level greater than 1.7 mmol / l, blood pressure greater than or equal to 130 mm Hg / 85 mm Hg, cholesterol level (HDL) less than 1.0 mmol / l, fasting blood glucose greater than or equal to 5.6 mmol / l),
* suffering from diabetes (even treated),
* during a slimming diet,
* during treatment with chemotherapy,
* with gastrointestinal pathology,
* with intolerance (milk, lactose, gluten ...) or a diet other than omnivorous (vegetarians, vegans, vegans),
* smoking more than 4 cigarettes / day,
* drinking more than 2 glasses of alcohol per day,
* refusing not to smoke, vape or remove a nicotine patch the morning of the samples,
* having a biological assessment judged by the investigator to be incompatible with the test,
* having a medical and / or surgical history judged by the investigator to be incompatible with the test,
* having drug treatments or nutritional supplements judged by the investigator to be incompatible with the test, (see detail in 8.5)
* having cooperation and understanding that does not allow strict compliance with the conditions set out in the protocol,
* participating in another clinical trial, or being in an exclusion period, or having received a total amount of compensation greater than 4500 euros over the 12 months preceding the start of the trial,
* benefiting from a legal protection measure (curatorship, guardianship, safeguard of justice),
* refusing to participate in the study.

Fragile elderly group:

Same non-inclusion criteria as above except modification on 2 criteria:

* Renal failure (clearance \<30 ml / min according to the CKD-EPI formula)
* No restriction on the parameters defining the metabolic syndrome unless the subject has treated insulin-dependent diabetes.

Primary outcomes:
measure: Evaluation of the bacterial population of the stool by analysis of the 16S rRNA gene
timeFrame: Day +7
Secondary outcomes:
measure: Measurement of muscular functional aptitudes with the Get up and Go muscular test scale
timeFrame: Day 0
measure: Measurement of muscular functional aptitudes with the Short Physical Performance Battery (SPPB) score
timeFrame: Day 0
measure: Evaluation of the the maximum voluntary force of manual gripping.
timeFrame: Day 0
measure: Evaluation of the voluntary level of autonomy with Functional Independence Measure (FIM) questionnaire
timeFrame: Day 0
measure: Measurement of the distance travelled in 6 minutes with the 6-minute walk test
timeFrame: Day 0
measure: Fat mass ratio determination
timeFrame: Day 0
measure: Lean mass ratio determination
timeFrame: Day 0
measure: Water mass ratio determination
timeFrame: Day 0
measure: Evaluation of the participant nutritional state with Mini Nutritional Assessment (MNA)
timeFrame: Day -7
measure: Evaluation of the participant cognitive state with Mini Mental State Examination (MMSE)
timeFrame: Day -7
measure: Plasma glucose dosage
timeFrame: Day -7
measure: Plasma creatinine dosage
timeFrame: Day -7
measure: Creatinine clearance
timeFrame: Day -7
measure: Plasma albumin dosage
timeFrame: Day -7
measure: Plasma total cholesterol dosage
timeFrame: Day -7
measure: Plasma High Density Lipoprotein cholesterol (HDL-chol) dosage
timeFrame: Day -7
measure: Plasma triglycerides dosage
timeFrame: Day -7
measure: Plasma liver enzymes (AST/ALT/GGT) dosage
timeFrame: Day -7
measure: Plasma phosphatase alkaline dosage
timeFrame: Day -7
measure: Plasma C-reactive protein dosage
timeFrame: Day -7
measure: Complete blood count (CBC)
timeFrame: Day -7
measure: Dosage of TNF-alpha allowing assessment of inflammatory status
timeFrame: Day -7
measure: Dosage of IL1 allowing assessment of inflammatory status
timeFrame: Day -7
measure: Dosage of IL6 allowing assessment of inflammatory status
timeFrame: Day -7
measure: Dosage of MCP1 allowing assessment of inflammatory status
timeFrame: Day -7
measure: Dosage of IL10 allowing assessment of inflammatory status
timeFrame: Day -7
measure: Dosage of LPS-binding protein allowing assessment of inflammatory status
timeFrame: Day -7
measure: Dosage of sDC14 allowing assessment of inflammatory status
timeFrame: Day -7
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Gisèle PICKERING
role: PRINCIPAL_INVESTIGATOR
References: