NCT07499167 - BRAHMS: Bed Rest And HypoMetabolism Study | Crick

Eligibility

Sex: MALEMin age: 20 YearsMax age: 40 YearsHealthy volunteers:

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Inclusion Criteria: * Healthy male volunteers (see below the description of medical tests and laboratory analysis performed at the selection visit) * Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination): in particular, free from any known chronic disease or any acute mood or eating disorder, infectious disease or cardiovascular, metabolic, neurological, ENT (especially orthostatic hypotension and vestibular disorders), orthopedic or musculoskeletal disorders. * 20 to 40 years old * 165 to 185 cm * Body Mass Index between 20 and 26 kg.m-2 * Stable body weight in the past 3 months (less than 4% change) * Fat Mass Index (FMI), defined as (bodyfat weigh in kg)/(height in m)2: between 3 and 6 kg.m-2, measured by whole-body DEXA * Triglyceride level under 1.7 mmol.L-1 * Normal bone mass density at left hip and lumbar spine: T-score\>-1.5, measured by DEXA * VO2peak/VO2max between 35 and 55 mL.min-1.kg-1 * Non-smokers * No alcohol or drug dependence, no medical treatment on a regular basis * Affiliated to a Social Security system and, for non-French resident, holding a European Health Insurance Card (EHIC) or a Global Health Insurance Card (GHIC). * Free of any engagement during the study * Who agreed to take part in the study and signed the informed consent Exclusion Criteria: * Any history or presence of clinically relevant chronic disease; any acute infectious disease. Particularly (but not limited to): * Symptomatic orthostatic hypotension whatever the decrease in blood pressure, or asymptomatic postural hypotension defined by a decrease in SBP equal to or greater than 20 mmHg within 3 minutes when changing from the supine to the standing position * Personal or family history of thrombosis, genetic mutation for factor V or prothrombin gene * Cardiac arrhythmia * Hypertension * Auto-immune diseases or Raynaud's syndrome * History or symptoms of sleep apnea * Chronic back pains, * Vertebral fracture, scoliosis, or herniated disc, * Color-blindness, * Self-reported hearing problems or binocular visual acuity under 6/10 after correction * Vestibular disorders * Drug addiction * History of migraines, * History of hiatus hernia or gastro-esophageal reflux, * History of thyroid dysfunction or diabetes * History of head trauma, * History of neurological diseases (e.g. epilepsy) * History of genetic muscle and bone diseases of any kind * Significant history of allergies * Significant abnormality in blood tests * Positive serology for hepatitis A, hepatitis B, hepatitis C or AIDS (HIV) virus * Mood and Eating disorder (current or past), screened with the Hospital Anxiety Depression Scale (HADS), SCOFF (Sick, Control, One, Fat, Food) and the Eating Disorder Examination Questionnaire (EDE-Q) * Antibiotics exposure 2 months prior to the study * Major lifestyle changes (e.g. significant weight/body changes, diet or exercises regimen) 6 months prior to the study * Specific diet (e.g vegan, carnivore, intermittent fasting, dietary supplements consumption) * History of hypocaloric diet, judged as significant by the investigator * Subject who, in the judgment of the investigator, is likely to be non-compliant during the study, or unable to cooperate because of a language problem or poor mental development, * Subject in the exclusion period of another clinical research, * Subject who received 6000 Euros or more within 12 months for being a research subject, * Poor tolerance to blood sampling, * Subject who cannot be contacted in case of emergency, * Contraindications for MRI: claustrophobia, presence of osteosynthesis material or metal implants, * Blood donation of more than 7 ml/kg in the 8 weeks prior to the start of the study, * Vulnerable people according to law "Code de la Santé Publique" (L1121-5 to L1121-8): * Pregnant or nursing women (urine pregnancy test for women of childbearing potential) * People deprived of their liberty by an administrative or judicial decision * People under involuntary psychiatric care * People admitted in a health or social establishment for purposes other than research * Minors * Adults subject to legal protection (subject under guardianship or trusteeship) or unable to express their consent

Outcomes

Primary Outcomes

Lean Body Mass

Lean Body Mass assessed by dual energy x-ray absorptiometry (DEXA)

Time frame: At baseline, during the ten days of intervention and until 90 days after the end of the intervention

Secondary Outcomes

Change in body fluid compartments by bioelectrical impedance analysis

Extracellular, intracellular and total body water (L) will be estimated by bioimpedance

Time frame: At baseline, during the ten days of intervention and until 90 days after the end of the intervention

Change in whole-body Magnetic Resonance Imaging (MRI)

Change in MRI-measured whole-body Lean mass (kg) and Fat mass (kg) will be estimated

Time frame: At baseline and at day 9 of intervention period

Change in mood

Change in mood is assessed using the Profile of Mood States (POMS) questionnaire. POMS questionnaire gives 6 measures of mood: Tension/anxiety, Depression, Anger/hostility Dynamism, Fatigue, Confusion A Total Mood Disturbance (TMD) score is calculated by summing the totals for the negative subscales (tension, depression, fatigue, confusion, anger) and then subtracting the totals for the positive subscale (vigor /esteem-related affect).

Time frame: At baseline, during the ten days of intervention and until 4 days after the end of the intervention

Assessment of movements by volunteers

Actigraphs attached to wristbands placed on the non-dominant wrist and ankle of each volunteer

Time frame: At baseline, during the ten days of the intervention and until 4 days after the end of the intervention

Change in cardiovascular deconditioning and orthostatic tolerance (stand test)

This test continuously measures heart rate (bpm) via a Finapres device while subjects sit for 5 minutes, then stand for 10 minutes and then sit again for 5 minutes

Time frame: At baseline and 1 day after the end of intervention period

Changes in orthostatic tolerance

Orthostatic tolerance will be assessed during a tilt test combined with Lower Body Negative Pressure test (LBNP test)

Time frame: At baseline and 1 day after the end of intervention period

Changes in peak aerobic power (VO2max test)

Exercise capacity wil be assessed by graded cycling on sitting ergometer until exhaustion

Time frame: At baseline and 4 days after the end of intervention period

Changes in plasma volume

Plasma volume (L) will be assessed by the Dill \& Costill method

Time frame: At baseline, during the ten days of the intervention and until 4 days after the end of the intervention

Change in long term blood pressure

This test continuously measures Blood Pressure during 24 hours with the SOMNOTouch device.

Time frame: At baseline, during the 10 days of the intervention, and 4 days after the end of the intervention

Change in macrocirculation

Macrocirculation will be assessed using standard ultrasound measurements at the carotid and femoral levels (arteries and veins).

Time frame: At baseline, during the 10 days of the intervention, and at 3 days after the end of the intervention

Change in endothelial function

The tests consists in the measurement of the variations of the brachial artery diameter as a response to shear stress.

Time frame: At baseline, during the 10 days of the intervention, and 3 days after the end of the intervention

Myofiber atrophy evaluation

Biopsy sampling from m. vastus lateralis will be performed to measure structure and function of muscle fibers.

Time frame: At baseline and at day 9 of intervention

Changes in jump performance

Jump performance will be assessed on a platform and height of the jump will be evaluated

Time frame: At baseline and 1 day after the end of the intervention

Change in protein metabolism

Labeled tracers (¹³C leucine for oxidation, ¹⁵N-phenylalanine for degradation, ²H₅-phenylalanine for synthesis monitoring and NaH13CO3 for quantification of amin acid oxidation) will be infused to the volunteers, and blood, urine, muscle and breath samples will be collected.

Time frame: At baseline and at day 9 of the intervention

Change in muscle strength

Muscle strength will be assessed via dynamometry

Time frame: At baseline and 2 days after the end of the intervention

Change in bone biological marker

Measuring bone-specific Alkaline Phosphatase (bAP) in blood

Time frame: At baseline, during the ten days of intervention and until 90 days after the end of the intervention

Changes in bone density (by High Resolution Peripheral Computed Tomography (HR-pQCT))

Bone density (g/cm2) is measured at tibia and radius level with HR-pQCT.

Time frame: At baseline and until 90 days after the end of the intervention

Changes in Resting Metabolic Rate (RMR)

RMR will be measured by indirect calorimetry technique

Time frame: At baseline, during the ten days of intervention and until 90 days after the end of the intervention

Change in nitrogen balance

Nitrogen balance is a measure of nitrogen input minus nitrogen output. Nitrogen intake is calculated with a nutrition software. Protein oxidation measured in the 24-Hour urine collection estimates nitrogen output.

Time frame: At baseline, during the ten days of intervention and at 90 days after the end of the intervention

Change in metabolic flexibility (Oral Glucose Tolerance Test (OGTT))

Metabolic flexibility will be measured during OGTT to assess the ability of the body to adjust energy substates' availability.

Time frame: At baseline and 4 days after the end of the intervention.

Change in glucose homeostasis

Continuous measurement of interstitial glucose concentration by Dexcom sensor

Time frame: From baseline to day 5 after the end of the intervention

Change in energy expenditure of tissues and organs (by PET-scan)

Regional mapping of metabolic activity by dynamic PET-scan with ¹⁸F-fluorodeoxyglucose

Time frame: At baseline and at day 7 of the intervention period

Metabolic change in adipose tissue

Histology, cell culture, adipocyte size distribution and whole adipose tissue transcriptome, proteome, lipidome and metabolome on adipose tissue biopsy

Time frame: At baseline and at day 9 of the intervention

Change in gut microbiota

Gut microbiome, metabolome and proteome will be measured in stool samples

Time frame: At baseline, during the ten days of the intervention and 4 days after the end of the intervention period

Modification of self perceived hunger

Questionnaires about self-perceived hunger will be delivered before and after breakfast, lunch, snack, and dinner, or at the equivalent times on the fasting days. The questionnaire consists of a Visual Analogue Scale on which the volunteer must indicate their level of hunger (from 'not at all' to 'extremely')

Time frame: At baseline, during the ten days of the intervention and until 4 days after the end of the intervention period

Change in energy requirements

Change in energy requirements using water labeled with a stable oxygen isotope (H218O)

Time frame: At baseline and at day 9 of the intervention period

Change in motor function (Sit-to-stand test)

Sit-to-stand test : volunteer will be requested to rise as fast as possible from a chair without using hands and stand for 10s. The following parameter will be measured : Settling time after standing.

Time frame: At baseline and 1 day after the end of the intervention period

Change in standing balance

This test assesses standing balance on a platform covered with 12-cm thick medium density foam.

Time frame: At baseline and 1 day after the end of the intervention period

Change in vestibular health

Battery of tests will be used to asses vestibular health: recovery from fall, path integration, distance perception, perception of self-rotation, how long 1', Posner task, antisaccade task

Time frame: At baseline and 1 day after the end of the intervention period

Change in cognitive state

This test monitor changes in the subject's emotional state and executive function by evaluatingpsychotechnical tasks on a laptop (the neurosensorybox) with physiological sensors (SOMNO HD system).

Time frame: At baseline, during the ten days of the intervention period and at day 5 after the end of the intervention

Salivary cortisol evolution

To characterize stress level, morning and evening salivary cortisol (ng/ml) will be assessed

Time frame: At baseline, at day 1, 3 & 10 of intervention period, and day 4 after the end of the intervention

Change in memory performance

Subjects are exposed to a series of images that will have to be remembered. After a delay of 1 hour or 24 hours they will be questioned on a series of images presented under the same conditions and they will have to indicate in a grid whether these images are known or new

Time frame: At baseline, during the ten days of the intervention period, and until 3 days after the end of the intervention

Change in the internal representation of 3D space

This tests consist in a rhythmic point-to-point hand movements in virtual reality.

Time frame: At baseline, during the ten days of the intervention period, and until 3 days after the end of the intervention

Change in gastro-brain interaction

Assessment of the correlation between gastric electrical activity (measured via Electrogastrography) and neural oscillatory responses (measured via Electroencephalography) during a cognitive task

Time frame: At baseline, during the ten days of the intervention period, and until 4 days after the end of the intervention

Change in motor function (Walk and turn test)

Walk and turn test : volunteer will be instructed to walk as quickly as possible straight ahead toward a cone walk around it and return to the chair. Completion time per walk-and-turn trial will be measured.

Time frame: At baseline and 1 day after the end of the intervention period

Change in motor function (Tandem Walk)

Tandem walk : Volunteer will walk 10 heel-to-toe steps with their arms folded across their chests and their eyes closed (3 trials) followed by one trial with their eyes open. Percentage of correct steps will be measured.

Time frame: At baseline and 1 day after the end of the intervention period

BRAHMS: Bed Rest And HypoMetabolism Study

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes