Clinical trial NCT06777329: A Comparison Study Between 10 Days of Dry Immersion Versus 10 Days of Head-down Bedrest on 20 Healthy Male Volunteers
Official title: Standardization of the Dry Immersion Model Used as a Ground-based Model to Mimic Weightlessness. Part 3: a Comparison Study Between 10 Days of Dry Immersion vs. 10 Days of Head-down Bedrest on 20 Healthy Male Volunteers (VIVALDI 3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Weightlessness Simulation
Keywords: Comparison of 2 weightlessness simulation models
Lead sponsor: Centre National d'Etudes Spatiales
Sponsor class: OTHER_GOV
First posted: 2025-01-15
Enrollment: 20
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The space agencies are actively engaged in studying the physiological adaptation to space environment through studies on board the International Space Station (ISS) but also on the ground. Different methods are used to simulate weightlessness on Earth, including cellular models, animal models using hind-limb unloading, or on humans with unilateral lower limb suspension. However, two approaches, -6° head-down bed rest (HDBR) and dry immersion (DI) have provided possibilities for long-term exposures with findings closest to those seen with a weightless state. They produce changes in body composition (including body fluid redistribution), cardiovascular and skeletal muscle characteristics that resemble the effects of microgravity.

The common physiological denominator is the combination of a cephalad shift of body fluids and reduced physical activity. Being similar in their effects on the human body, these models, however, differ in their specifics and acting factors.

The Head-down Bedrest (HDBR) model has been widely used for this purpose and is considered one of the references for reproducing the physiological effects of weightlessness on Earth. During HDBR, subjects are lying down with an angle of -6° between the feet and head, on their side, their back or their front, but must keep one shoulder in contact with the mattress. All daily activities and tests are performed in this position.

One of the advantages of the HDBR model is that it has now been used in a great number of studies internationally, and its effects have long been described and compared with those of microgravity and spaceflight. Long-term bedrest is the gold-standard method for studying the effects of weightlessness and to test countermeasures.

Dry immersion involves immersing the subject in water covered with an elastic waterproof fabric. As a result, the immersed subject, who is freely suspended in the water mass, remains dry. Within a relatively short duration, the model can faithfully reproduce most physiological effects of actual microgravity, including centralization of body fluids, support unloading, and hypokinesia.

The objective of the present study is to compare the physiological adaptations to10 days of dry immersion versus 10 days of head-down bedrest in 20 healthy male subjects. A set of measurements will assess the changes in the cardiovascular, neuro-ophthalmological, hematological, metabolic, sensorimotor, immune, muscle and bone systems as a result of both models. The most likely outcome of this study will not be to show a clear superiority of one model over the other. Rather, we expect to show differences in kinetics and intensity of adaptations, that should vary from one system to another. This will help future researchers choose the best model depending on the system they are investigating and the rapidity or intensity of the effect they are exploring. The two models, instead of competing with one another, are probably complementary.


Eligibility criteria: * Healthy male volunteer (see below the description of medical tests and laboratory analysis performed at the selection visit),
* Age 20 to 40,
* No overweight nor excessive thinness with BMI (weight kg/ height m2) between 20 and 26,
* Height between 165cm and 180 cm,
* Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination): in particular, free from any chronic disease or any acute infectious disease or cardiovascular, neurological, ENT (especially orthostatic hypotension and vestibular disorders), orthopaedic or musculoskeletal disorders,
* Fitness level assessment: 35 ml/min./kg \< VO2max \< 55 ml/min./kg,
* Non active smokers,
* No alcohol, or drug addiction, and no medical treatment,
* Covered by a Health Insurance System,
* Having signed the informed consent,
* Free from any engagement during the study.

Exclusion Criteria:

* Any history or presence of clinically relevant cardiovascular, neurological or ENT (especially orthostatic hypotension and vestibular disorders), any chronic disease; any acute infectious disease. Particularly:
* 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,
* Cardiac rhythm disorders,
* Hypertension,
* Chronic back pains,
* Vertebral fracture, scoliosis or herniated disc,
* Glaucoma,
* Self-reported hearing problems,
* History of migraines,
* History of hiatus hernia or gastro-esophageal reflux,
* History of thyroid dysfunction, renal stones, diabetes,
* History of head trauma,
* History of genetic muscle and bone diseases of any kind,
* Past records of thrombophlebitis, family history of thrombosis or positive response in thrombosis screening procedure (anti thrombin III, S-protein, C-protein, factor V Leiden mutation and the mutation 20210 of the prothrombin gene),
* Signs of venous insufficiency, varicose veins, or telangiectasia
* Bone mineral density: T-score ≤ -1.5,
* Poor tolerance to blood sampling,
* Having given whole blood (more than 7ml/kg) in a period of 8 weeks or less before the start of the experiment, or having given whole blood more than 5 times in the past 12 months,
* Significant history of allergy, especially no dermatological allergy,
* History of food allergy,
* Significant anomaly detected in the biological analysis,
* Positive reaction to any of the following tests: HVA IgM (hepatitis A), HBs antigen (hepatitis B), anti-HVC antibodies (hepatitis C), anti-HIV1+2 antibodies,
* Vegetarian or vegan,
* Refusal to give permission to contact his general practitioner,
* 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 already participating or in the exclusion period of a clinical research,
* Subject who has received more than 6000 Euros within 12 months for being a research subject,
* MRI contraindications:
* History or active claustrophobia,
* Osteosynthesis material, presence of metallic implants or any other contra-indication for MRI,
* Allergy to Gadolinium.
* Vulnerable persons according to law "Code de la Santé Publique" (L1121-5 to L1121-8) :
* Persons deprived of their liberty by an administrative or judicial decision,
* Persons under involuntary psychiatric care,
* Persons 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.

Primary outcomes:
measure: Changes in orthostatic tolerance
timeFrame: At baseline and first day of recovery
measure: Changes in peak aerobic power (VO2max test)
timeFrame: At baseline and the first day of recovery
measure: Change in plasma volume
timeFrame: At baseline and 3 days after the end of the intervention
measure: Change in plasma volume percentage
timeFrame: At baseline and at day 1, day 3, day 7 and at the end of the intervention periods
measure: Change in fluid shift distribution towards the cardiac and cephalic region
timeFrame: At baseline, the first day to quantify the short term effect, the fifth day and the tenth day of interventions to quantify the long term effect of fluid shift
measure: Change in body fluid compartments by bioelectrical impedance analysis
timeFrame: At baseline, during the ten days of intervention and until 3 days after the end of the intervention
measure: Change in calf and thigh circumferences
timeFrame: At baseline, during the intervention period and until 3 days after the intervention period
measure: Change in fat and lean body mass measured by dual energy x-ray absorptiometry (DEXA)
timeFrame: At baseline, after 10 days of dry-immersion and 10 days of reovery
measure: Change in Resting Metabolic Rate (RMR)
timeFrame: At baseline, at day 3 and day 9 days of intervention periods
measure: Change in nitrogen balance
timeFrame: At baseline, at day 3 and day 9 days of intervention periods
measure: Change in glucose tolerance (Oral Glucose Tolerance Test)
timeFrame: At baseline, at day 3 and day 9 days of intervention periods
measure: Change in serum bone formation marker (bone-specific Alkaline Phosphatase bAP)
timeFrame: At baseline and during the 10 days of interventions
measure: Change in serum bone resorption marker (C-terminal cross-linked telopeptide of type I collagen CTx)
timeFrame: At baseline and during the 10 days of interventions
measure: Changes in bone density (by DEXA and High Resolution Peripheral Computed Tomography (HR-pQCT))
timeFrame: At baseline and at day 10 of intervention periods
measure: Change in serum cartilage synthesis biomarkers
timeFrame: At baseline, during the intervention period and until 3 days after the intervention period
measure: Change in serum cartilage degradation biomarkers
timeFrame: At baseline, during the intervention period and until 3 days after the intervention period
measure: Change in muscle strength
timeFrame: At baseline and after one day of recovery
measure: Changes in jump performance
timeFrame: At baseline and the first day of recovery
measure: Change in contraction time
timeFrame: At baseline and at the end of the intervention periods
measure: Change in standing balance
timeFrame: At baseline and at day 1 and day 2 of recovery
measure: Change in walking balance
timeFrame: At baseline and after 10 days of intervention and day 1 after the end of the intervention
measure: Change in height
timeFrame: At baseline and at day 1, day 2 and day 3 of recovery
measure: Change in mid cerebral artery (MCA) blow flow velocity
timeFrame: At baseline and one day after the intervention period
measure: Change in circadian rhythms of blood pressure
timeFrame: At baseline and during the ten days of the intervention periods
measure: Change in mood
timeFrame: At baseline, at day 5 of the intervention period and 3 days after the end of the intervention
measure: Change in affective states
timeFrame: At baseline, at day 5 of the intervention period and 3 days after the end of the intervention
measure: Change in sleep quality
timeFrame: Daily from baseline to 10 days after the end of the intervention
measure: Change in psychological state: mental health
timeFrame: At baseline, at day 5 of the intervention period and 4 days after the end of the intervention
measure: Change in coping strategies
timeFrame: At day 5 of the intervention and 2 days after the end of the intervention
measure: Measurement of changes in subjective sleepiness
timeFrame: At baseline, at day 4 and 8 of the intervention period and 3 days after the end of the intervention
measure: Change in circadian variations of heart rate
timeFrame: At baseline, at day 1, day 4, day 7 of intervention, and at first day of recovery
measure: Change in daily body movements
timeFrame: Continuously from baseline until 5 days after the intervention period
measure: Dynamics of body fluids during the 4 first hours of exposure
timeFrame: The 4 first hours of Dry Immersion / Bed Rest
measure: Lower limb vascular properties
timeFrame: At baseline, at day 10 of intervention periods, and day 3 of recovery
measure: Myofiber atrophy
timeFrame: At baseline and at day 8 of intervention
measure: Post-occlusive reactive hyperemia at great toe and thumb level
timeFrame: At baseline and 4 days after the end of the intervention
measure: Quantitative sensory testing at the dorsum of the foot (vibration detection threshold)
timeFrame: At baseline, at day 7 of intervention periods, and day 2 of recovery
measure: Whole-body MRI
timeFrame: At baseline, at day 9 of intervention periods
measure: Vestibular health evaluation
timeFrame: At baseline and the first day of recovery
measure: Blood cytokines evolution
timeFrame: At baseline, at day 3 & 10 of intervention periods, and day +10 of recovery
measure: Salivary cortisol evolution
timeFrame: At baseline, at day 1, 3 & 10 of intervention periods, and day +4 & +10 of recovery
measure: Change in optic nerve sheath diameter (ONSD) considered as an indirect marker for intracranial pressure (ICP) estimation
timeFrame: From baseline to 1 day after the end of the intervention
measure: Change in intraocular pressure (IOP)
timeFrame: From baseline to 1 day after the end of the intervention
measure: Change in visual acuity
timeFrame: At baseline and 2 days after the intervention period
measure: Change in visual field
timeFrame: At baseline and 2 days after the intervention period
measure: Change in the anatomical characteristics of the eye (optical biometry)
timeFrame: At baseline and 2 days after the intervention period
measure: Change in the central corneal thickness
timeFrame: At baseline and 2 days after the intervention period
measure: Change in the retina by non-mydriatic fundus retinography
timeFrame: At baseline and 2 days after the intervention period
measure: Change in the cornea topography
timeFrame: At baseline and 2 days after the intervention period
measure: Change in cerebral structures and in venous circulation of the brain by MRI
timeFrame: At baseline and at day 9 of intervention
measure: Change in thrombotic and fibrinolytic processes
timeFrame: At baseline, during the intervention and 2 days after the intervention period
measure: Change in energy requirements
timeFrame: At baseline and at day 2 of the intervention period
measure: Change in skin microcirculation
timeFrame: At baseline and 3 days after the intervention period
measure: Change in cardiovascular deconditioning and orthostatic tolerance (stand test)
timeFrame: At baseline and 2 days after the intervention period
measure: Change in stress and mental load
timeFrame: From baseline to 10 days after the end of the intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Medes-Institut de Médecine et de Physiologie Spatiale
Study officials:
affiliation: University Hospital, Angers
name: Marc-Antoine CUSTAUD, MD, PhD
role: STUDY_DIRECTOR
References: