A Comparison Study Between 10 Days of Dry Immersion Versus 10 Days of Head-down Bedrest on 20 Healthy Male Volunteers

NCT06777329 | Completed

• 2 other identifiers: 24-3362024-A02109-38
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Weightlessness Simulation

Keywords

Comparison of 2 weightlessness simulation models

Outcome Measures

Primary Outcomes (55)

• Changes in orthostatic tolerance

  Orthostatic tolerance (min) will be assessed during a progressive Lower Body Negative Pressure test (LBNP test)

  At baseline and first day of recovery

• Changes in peak aerobic power (VO2max test)

  Exercise capacity (ml/kg/min) wil be assessed by graded cycling on sitting ergometer until exhaustion

  At baseline and the first day of recovery

• Change in plasma volume

  Plasma volume (L) will be assessed by the carbon monoxide-rebreathing method

  At baseline and 3 days after the end of the intervention

• Change in plasma volume percentage

  The percentage change in plasma volume versus baseline (%) will be assessed by the Dill and Costill method

  At baseline and at day 1, day 3, day 7 and at the end of the intervention periods

• Change in fluid shift distribution towards the cardiac and cephalic region

  The consequences of the fluid shift on the cardiac and cephalic area will be assessed by quantifying the carotid and femoral diameters (mm), as well as the carotid intima media thickness (mm) by ultrasound.

  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

• Change in body fluid compartments by bioelectrical impedance analysis

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

  At baseline, during the ten days of intervention and until 3 days after the end of the intervention

• Change in calf and thigh circumferences

  Change in calf and thigh circumferences will be measured using a measuring tape (cm)

  At baseline, during the intervention period and until 3 days after the intervention period

• Change in fat and lean body mass measured by dual energy x-ray absorptiometry (DEXA)

  Change in fat and lean body mass (g) measured by dual energy x-ray absorptiometry (DEXA)

  At baseline, after 10 days of dry-immersion and 10 days of reovery

• Change in Resting Metabolic Rate (RMR)

  RMR (kcal/24h) will be measured by indirect calorimetry technique

  At baseline, at day 3 and day 9 days of intervention periods

• Change in nitrogen balance

  Nitrogen balance is a measure of nitrogen input minus nitrogen output. Nitrogen intake (g) is calculated with a nutrition software. Total urinary nitrogen (g) in the 24-Hour urine collection estimates nitrogen output

  At baseline, at day 3 and day 9 days of intervention periods

• Change in glucose tolerance (Oral Glucose Tolerance Test)

  Glucose (mmol/L) levels will be measured at baseline (fasting) and 30, 60, 90, 120 and 180 minutes after drinking within 5 min a water solution containing 75 g of glucose

  At baseline, at day 3 and day 9 days of intervention periods

• Change in serum bone formation marker (bone-specific Alkaline Phosphatase bAP)

  Change in bone-specific Alkaline Phosphatase (bAP, µg/L) will be assessed by chemiluminescence immunoassay

  At baseline and during the 10 days of interventions

• Change in serum bone resorption marker (C-terminal cross-linked telopeptide of type I collagen CTx)

  Change in C-terminal cross-linked telopeptide of type I collagen (CTx, pmol/L) will be assessed by chemiluminescence immunoassay will be assessed by enzyme-immmuno assay

  At baseline and during the 10 days of interventions

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

  Bone density (g/cm2) is measured at lumbar and hip level with DEXA and at tibia and radius level with HR-pQCT. Additionally tibia mechanical properties will be estimated by cortical ultrasound propagation velocity (m/s) via intraosseous ultrasonography.

  At baseline and at day 10 of intervention periods

• Change in serum cartilage synthesis biomarkers

  Change in serum CP II and in human cartilage glycoprotein-39 (YKL-40) concentrations

  At baseline, during the intervention period and until 3 days after the intervention period

• Change in serum cartilage degradation biomarkers

  Change in serum Cartilage Oligomeric Matrix Protein (COMP) and fragments or propeptide of type II collagen (C2C, C1,2C, Coll-2-1) concentrations

  At baseline, during the intervention period and until 3 days after the intervention period

• Change in muscle strength

  Muscle strength will be assessed from single leg isometric maximal voluntary contraction on the knee extensors \& flexors, the plantarflexors and dorsiflexors. The Isometric Torque will be measured in Nm. The peak of the three maximal attempts will be recorded for strength measures

  At baseline and after one day of recovery

• Changes in jump performance

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

  At baseline and the first day of recovery

• Change in contraction time

  Contraction time will be assessed during a measurement using the tensiomyography method in the following muscles: vastus lateralis, Gastrocnemius medialis and Biceps femoris of dominant leg.

  At baseline and at the end of the intervention periods

• Change in standing balance

  Standing balance (CoP velocity, mm/s) will be assessed by posturography eyes open and eyes closed on a platform covered with 12-cm thick medium density foam

  At baseline and at day 1 and day 2 of recovery

• Change in walking balance

  Functional mobility test (such as sit and walk, heel to toe steps with eyes closed and open, Triangle Completion Task) will assess walking balance.

  At baseline and after 10 days of intervention and day 1 after the end of the intervention

• Change in height

  Change in height (mm) measured in standing position

  At baseline and at day 1, day 2 and day 3 of recovery

• Change in mid cerebral artery (MCA) blow flow velocity

  Mid cerebral artery (MCA) blow flow velocity will be measured by transcranial Doppler

  At baseline and one day after the intervention period

• Change in circadian rhythms of blood pressure

  Continuous 24-h recording of systolic and diastolic blood pressure will be performed by a Non Invasive Blood Pressure system (SOMNOtouch™NIBP) designed for ambulatory continuous measurements

  At baseline and during the ten days of the intervention periods

• Change in mood

  Change in mood is assessed using the Profile of Mood States (POMS) questionnaire, by calculation of total mood disturbance (scale from -32 to 200, a higher score indicates more severe mood disturbance)

  At baseline, at day 5 of the intervention period and 3 days after the end of the intervention

• Change in affective states

  Positive and Negative Affect Schedule (PANAS) questionnaire will be used to assess the intensity of positive (range from 10 to 50, with higher scores representing higher levels of positive affect) and negative (range from 10 to 50, with lower scores representing lower levels of negative affects) affective states. PANAS self-report questionnaire consists of two 10-item scales to measure both positive and negative affects.

  At baseline, at day 5 of the intervention period and 3 days after the end of the intervention

• Change in sleep quality

  Pittsburgh Sleep Dairy (PghSD) will be used to assess sleep perceived quality. The PghSD is an instrument with separate components to be completed at bedtime and waketime. The following parameters are registered or assessed: Bedtime, waketime, sleep latency, wake after sleep onset, total sleep time, mode of awakening and ratings of sleep quality, mood, and alertness on wakening, as well as daytime information on naps, exercise, meals and caffeine, tobacco and medications use.

  Daily from baseline to 10 days after the end of the intervention

• Change in psychological state: mental health

  ical well-being and capture distress GHQ-28 gives an overall total score and 4 scores for 4 subscales: Somatic symptoms, Anxiety/insomnia, Social dysfunction, Severe depression. Higher scores indicate higher levels of distress

  At baseline, at day 5 of the intervention period and 4 days after the end of the intervention

• Change in coping strategies

  Brief Cope Questionnaire is designed to measure effective and ineffective ways to cope with a stressful life event, and will be used to assess coping strategies. The Brief Cope is a shortened form (28 items) of the Carver and Scheier COPE inventory. There are 14 coping strategies. These strategies can be then gathered in two main categories : approach coping and avoidance coping.

  At day 5 of the intervention and 2 days after the end of the intervention

• Measurement of changes in subjective sleepiness

  Changes in subjective level of sleepiness will be measured using the Karolinska sleepiness scale (KSS) two times per day, with a scale from 1 to 10 (higher scores reprensent higher sleepiness).

  At baseline, at day 4 and 8 of the intervention period and 3 days after the end of the intervention

• Change in circadian variations of heart rate

  Difference between day-time and night-time heart rate (bpm) will be calculated

  At baseline, at day 1, day 4, day 7 of intervention, and at first day of recovery

• Change in daily body movements

  Accelerometry-derived daily physical activity counts will be quantified using actigraph GT3X+

  Continuously from baseline until 5 days after the intervention period

• Dynamics of body fluids during the 4 first hours of exposure

  Changes from pre to 240 min of exposure for plasma volume percentage versus baseline (%) assessed by the Dill and Costill method

  The 4 first hours of Dry Immersion / Bed Rest

• Lower limb vascular properties

  Change in tibial intracortical blood flow velocity (mm/s), induced by physiological maneuvers (velocity of intracortical blood flow at medial tibia level and its responses to vascular occlusion will be assessed via Ultrasound Vector Flow Mapping)

  At baseline, at day 10 of intervention periods, and day 3 of recovery

• Myofiber atrophy

  Biopsy sampling from m. vastus lateralis will be performed. Myofiber CSA related to fiber type (µm2) will be measured by morphometric analysis.

  At baseline and at day 8 of intervention

• Post-occlusive reactive hyperemia at great toe and thumb level

  Blood flow (AU) will be assessed via Laser Doppler flowmetry. Post-occlusive reactive hyperemia index will be calculated.

  At baseline and 4 days after the end of the intervention

• Quantitative sensory testing at the dorsum of the foot (vibration detection threshold)

  Vibration detection threshold (s) will be measured using graded tuning fork

  At baseline, at day 7 of intervention periods, and day 2 of recovery

• Whole-body MRI

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

  At baseline, at day 9 of intervention periods

• Vestibular health evaluation

  Battery of tests routinely performed on astronauts will be used. Sit-to-stand time (s) will be quantified.

  At baseline and the first day of recovery

• Blood cytokines evolution

  To characterize immune functions, the following blood cytokines (pg/ml) will be assessed: TPO, G-CSF, IL-1β, IL-1Ra, IL-4, IL-6, IL-8, IL-10, IFNy, TNF

  At baseline, at day 3 & 10 of intervention periods, and day +10 of recovery

• Salivary cortisol evolution

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

  At baseline, at day 1, 3 & 10 of intervention periods, and day +4 & +10 of recovery

• Change in optic nerve sheath diameter (ONSD) considered as an indirect marker for intracranial pressure (ICP) estimation

  The optic nerve sheath diameter (ONSD) variations will be measured by echography

  From baseline to 1 day after the end of the intervention

• Change in intraocular pressure (IOP)

  IOP measured by applanation

  From baseline to 1 day after the end of the intervention

• Change in visual acuity

  Far and near visual acuity are tested uncorrected, or if applicable with own correction with digital acuity system

  At baseline and 2 days after the intervention period

• Change in visual field

  Visual field measured by standard automated perimetry

  At baseline and 2 days after the intervention period

• Change in the anatomical characteristics of the eye (optical biometry)

  Optical biometry measured by partial coherence interferometry

  At baseline and 2 days after the intervention period

• Change in the central corneal thickness

  Central corneal thickness on a single point on the cornea measured by Ultrasonic pachymetry

  At baseline and 2 days after the intervention period

• Change in the retina by non-mydriatic fundus retinography

  Non-mydriatic fundus retinography allows a fundus photography to be taken and thus a color image of the papilla, retinal vessels and macula

  At baseline and 2 days after the intervention period

• Change in the cornea topography

  Cornea topography measured by corneal topography equipment (like Pentacam). The elevation topography according to Scheimpflug principle allows the mapping of the anterior and posterior surface of the cornea.

  At baseline and 2 days after the intervention period

• Change in cerebral structures and in venous circulation of the brain by MRI

  Visualization of cerebral structures and intracranial venous system will be performed by MRI coupled with injection of gadolinium

  At baseline and at day 9 of intervention

• Change in thrombotic and fibrinolytic processes

  Thrombotic and fibrinolytic processes will be assessed by thromboelastometry (TEM, coagulation analyzer from Matel Medizintechnik, Graz, Austria), providing a kinetic analysis of the clot formation process and of clot dissolution by the fibrinolytic system. Clotting time (min) wil be measured.

  At baseline, during the intervention and 2 days after the intervention period

• Change in energy requirements

  Change in energy requirements using the doubly labelled water

  At baseline and at day 2 of the intervention period

• Change in skin microcirculation

  Indirect evaluation of cardiovascular and neurovascular change by performing deep inspiration. Blood flow (AU) at great toe will be assessed via Laser Doppler flowmetry. Inspiratory gasp vascular response (%) will be calculated.

  At baseline and 3 days after the intervention period

• 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 5 minutes and then sit again for 5 minutes

  At baseline and 2 days after the intervention period

• Change in stress and mental load

  This test assesses the effects of dry immersion and bed rest on cognitive tasks involving various executive functions (e.g., attention, memory, decision-making) by assessing both physiological (via the SOMNO HD system) and behavioral parameters (e.g., emotions, cognitive load) using the D2 test of attention. Pourcentage of errors (%) will be measured as a qualitative aspect of performance.

  From baseline to 10 days after the end of the intervention

Study Arms (2)

Dry Immersion arm

EXPERIMENTAL

10 days of dry immersion

Behavioral: 10 days of dry immersion

Bed rest arm

EXPERIMENTAL

10 days of head down bed rest

Behavioral: 10 days of Head Down Bed Rest

Interventions

10 days of dry immersion BEHAVIORAL

The volunteers in this arm will be immersed up to the neck for 10 days in a specially designed bath filled with tap water.

Also known as: Dry Immersion (DI)

Dry Immersion arm

10 days of Head Down Bed Rest BEHAVIORAL

The volunteers in this arm will spend 10 days in -6° head down bed rest.

Also known as: Head Down Tilt (HDT)

Bed rest arm

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre National d'Etudes Spatiales: lead

Study Sites (1)

Medes-Institut de Médecine et de Physiologie Spatiale

Toulouse, France, 31400, France

Location

MeSH Terms

Interventions

Head-Down Tilt

Intervention Hierarchy (Ancestors)

Posture; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Marc-Antoine CUSTAUD, MD, PhD

  University Hospital, Angers

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2024
• First Posted: January 15, 2025
• Study Start: December 9, 2024
• Primary Completion: April 23, 2025
• Study Completion: April 23, 2025
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

FR (1)