Clinical trial NCT03915457: Thigh Cuffs to Prevent the Deconditioning Induced by 5 Days of Dry Immersion
Official title: Effects of Thigh Cuffs to Prevent the Deconditioning Induced by 5 Days of Dry Immersion Used as a Ground-based Model to Study the Effects of Weightlessness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Weightlessness
Weightlessness; Adverse Effect
Keywords: Simulated Microgravity
Weightlessness
Countermeasure
Dry immersion
Supportlessness
Lead sponsor: Centre National d'Etudes Spatiales
Sponsor class: OTHER_GOV
First posted: 2019-04-16
Enrollment: 20
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A monocentric open parallel randomized and controlled study.
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of the study is to investigate whether thigh cuffs help to prevent and/or reduce the deconditioning induced by 5 days of dry immersion and in particular the fluid shift and its related ophthalmological disorders. During a randomized 5 day dry-immersion study in 20 healthy male adults the two following aims will be undertaken:

* Ten scientific protocols will assess the changes in the cerebral, ocular, cardiovascular, metabolism, cognitive, muscle and bone systems.
* In the above mentioned systems, the potential beneficial effects of the countermeasure protocol will also be investigated.

Detailed description: Space flights have shown the possibilities and limitations of human adaptation to space. For the last 50 years, results showed that the space environment and microgravity in particular, cause changes that may affect the performance of astronauts. These physiological changes are now better known: prolonged exposure to a weightlessness environment can lead to significant loss of bone, muscle mass, strength, cardiovascular and sensory-motor deconditioning, immune, hormonal and metabolism changes. Nevertheless, more recent missions have revealed a new suite of physiological adaptations and consequences of space flight. Indeed, astronauts exposed to prolonged weightlessness experience hyperopic shifts and structural alteration in the eye (e.g., choroidal folds and optic disc edema). This condition was defined by NASA as Spaceflight-Associated Neuro-ocular Syndrome (SANS). Some of these vision changes remain unresolved for years after flight. This phenomenon has most likely existed since the beginning of human space flight, but is just recently being recognized as a major consequence of adaptation to microgravity. Changes in vision and eye structure are thought to be the result of prolonged exposure to space flight-induced headward fluid shifts and elevated intracranial pressure. Loss of the hydrostatic pressure gradient during spaceflight leads to this redistribution of body fluids toward the head. To prepare for future manned missions beyond the low Earth Orbit, the mechanisms underlying SANS syndrome have to be investigated and countermeasures designed to reverse or prevent SANS are required. Venoconstrictive thigh cuffs (VTCs) represent one possible countermeasure to mitigate a headward fluid shift. The Russian Space Agency uses VTCs (bracelets) to sequester fluid in the lower limbs and mitigate the subjective sensation of head congestion during space-flight. Moreover, experiments on 6-month Mir missions demonstrated that bracelets reduced jugular vein cross-sectional area in cosmonauts by 12% to 20%. However, it is unknown how VTCs (including bracelets) affect ocular physiologic features. The space agencies are actively engaged in studying the initiation and progression of SANS syndrome through studies on the International Space Station and on the ground. Indeed, considering the limited number of flight opportunities, the difficulties related to the performance of in-flight experiments (operational constraints for astronauts, limited capabilities of in-flight biomedical devices), ground-based experiments simulating the effects of weightlessness are used to better understand the mechanisms of physiological adaptation, design and validate the countermeasures. Different methods are used to simulate microgravity on Earth. However, two separate 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. Unlike bed rest, dry immersion provides a unique opportunity to study the physiological effects of the lack of a supporting structure for the body. Dry immersion means immersing into the thermoneutral water covered with special elastic free floating waterproof fabric. The subject, surrounded by film and "free suspended" in the water mass, remains dry. During horizontal immersion, pressure forces are distributed nearly equally around the entire surface of the body (only the head and neck are not entirely supported by water). The absence of mechanical support of specific zones during immersion creates a state akin to weightlessness that is called "supportlessness". Physiological changes under DI develop more rapidly and are more profound than under HDBR. This advanced ground-based model is extremely suited to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies.

The present study is organized in this context by the French space agency (CNES) to assess on twenty healthy male volunteers the effects of thigh cuffs to prevent the deconditioning induced by 5 days of dry immersion and in particular the fluid shift and its related ophthalmological disorders. Using an integrated approach, the CNES has selected ten scientific protocols to assess the changes in the different physiological fields and the potential beneficial effects of the countermeasure to prevent and/or reduce these changes.

Eligibility criteria: Inclusion Criteria:

* Healthy male volunteer (see below the description of medical tests and laboratory analysis performed at the selection visit),
* Age 20 to 45,
* No overweight nor excessive thinness with BMI (weight Kg/ height m2) between 20 and 26,
* Height between 158 and 185 cm,
* No personal nor family past record of chronic or acute disease or psychological disturbances which could affect the physiological data and/or create a risk for the subject during the experiment,
* Fitness level assessment:

  * if age \< 35 years: 35 ml/min/kg \< VO2max \< 60ml/min/kg
  * if age \> 35 years: 30 ml/min/kg \< VO2max \< 60ml/min/kg
* Walking between 7000 - 8000 steps/day,
* Active and free from any orthopedic (in particular no vertebral fracture, scoliosis or herniated disc) musculoskeletal and cardiovascular disorders,
* Non smokers,
* No alcohol, no drug dependence and no medical treatment,
* No antibiotic treatment in the 2 previous months before the beginning of the study,
* Covered by a Social Security system,
* Have signed the information consent,
* Free of any engagement during the study.

Exclusion Criteria:

* - Past record of orthostatic intolerance,
* Cardiac rhythm disorders,
* Chronic back pains,
* Vertebral fracture, scoliosis or herniated disc,
* Glaucoma,
* HTA,
* History of migraines,
* History of hiatus hernia or gastro-esophageal reflux,
* History of thyroid dysfunction, renal stones, diabetes,
* History of head trauma,
* 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),
* Individuals exhibiting mutations involved in hereditary hemochromatosis (HAMP, HFE, HFE2, SCL40A1 and TRF2),
* Abnormal result for lower limbs echo-doppler,
* History or active claustrophobia,
* History of genetic muscle and bone diseases of any kind,
* Bone mineral density: T-score ≤ -1.5 on the hip,
* Osteosynthesis material, presence of metallic implants or any other contra-indication for MRI,
* Poor tolerance to blood sampling,
* Having given blood (more than 8ml/kg) in a period of 8 weeks or less before the start of the experiment,
* Antibiotic treatment in the 2 previous months before the beginning of the study,
* Vegetarian or vegan,
* History of food allergy,
* 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,
* Subject already participating or in the exclusion period of a clinical research,
* Refusal to give permission to contact his general practitioner,
* Incarcerated persons,
* 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 who has received more than 4500 Euros within 12 months for being a research subject.
* Subject under guardianship or trusteeship.

Primary outcomes:
measure: Change in optic nerve sheath diameter (ONSD) considered as an indirect marker for intracranial pressure (ICP) estimation
timeFrame: Baseline and five days of dry-immersion
Secondary outcomes:
measure: Change in the optic nerve fibers thickness
timeFrame: Baseline and five days of dry-immersion
measure: Change in cerebral structures and in venous circulation of the brain by MRI
timeFrame: Baseline and five days of dry-immersion
measure: Change in cerebral perfusion
timeFrame: Baseline and five days of dry-immersion
measure: Change in intraocular pressure.
timeFrame: Baseline and five days of dry-immersion
measure: Change in orthostatic tolerance
timeFrame: Baseline and five days of dry-immersion
measure: Change in body fluid compartments by bioelectrical impedance analysis
timeFrame: Baseline and during five days of dry-immersion
measure: Change in circadian rhythms of blood pressure
timeFrame: Baseline and during the five days of the dry-immersion period
measure: Measurement of the fluid shift towards the cephalic region by ultrasound
timeFrame: The first day to quantify the short term effect and the fourth day of dry-immersion to quantify the long term effect of fluid shift
measure: Change of whole-body and skeletal muscle metabolic flexibility (i.e. capacity to adapt fuel oxidation to fuel availability)
timeFrame: Baseline and 4 days of dry-immersion
measure: Change in expression pattern of atrophic and phenotypic modifiers in skeletal muscle
timeFrame: Baseline and 5 days of dry-immersion
measure: Change in muscle transcriptome profile
timeFrame: Baseline and 5 days of dry-immersion
measure: Measurement of muscle contractile properties using skinned fibers
timeFrame: Baseline and 5 days of dry-immersion
measure: Measurement of fat cell invasion into skeletal muscle
timeFrame: Baseline and 5 days of dry-immersion
measure: Change in the balance of bone remodeling markers
timeFrame: Baseline, during and after 5 days of dry-immersion
measure: Change in the composition of the intervertebral disc (IVD).
timeFrame: Baseline and 5 days of dry-immersion
Other outcomes:
measure: Change in gut microbiota
timeFrame: Baseline, during and after 5 days of dry-immersion
measure: Change in iron metabolism
timeFrame: Baseline, during and after 5 days of dry-immersion
measure: Change in the contribution of visual and vestibular information used while performing mental transformations during a perspective-taking task.
timeFrame: Baseline, during and after 5 days of dry-immersion
measure: Change in own-body representation.
timeFrame: Baseline, during and after 5 days of dry-immersion
Locations:
city: Toulouse
country: France
facility: Medes-Imps
Study officials:
References:
citation: Arbeille P, Herault S, Fomina G, Roumy J, Alferova I, Gharib C. Influences of thigh cuffs on the cardiovascular system during 7-day head-down bed rest. J Appl Physiol (1985). 1999 Dec;87(6):2168-76. doi: 10.1152/jappl.1999.87.6.2168.
citation: Balasubramanian S, Tepelus T, Stenger MB, Lee SMC, Laurie SS, Liu JHK, Feiveson AH, Sadda SR, Huang AS, Macias BR. Thigh Cuffs as a Countermeasure for Ocular Changes in Simulated Weightlessness. Ophthalmology. 2018 Mar;125(3):459-460. doi: 10.1016/j.ophtha.2017.10.023. Epub 2017 Nov 16. No abstract available.
citation: De Abreu S, Amirova L, Murphy R, Wallace R, Twomey L, Gauquelin-Koch G, Raverot V, Larcher F, Custaud MA, Navasiolava N. Multi-System Deconditioning in 3-Day Dry Immersion without Daily Raise. Front Physiol. 2017 Oct 13;8:799. doi: 10.3389/fphys.2017.00799. eCollection 2017.
citation: Kermorgant M, Leca F, Nasr N, Custaud MA, Geeraerts T, Czosnyka M, Arvanitis DN, Senard JM, Pavy-Le Traon A. Impacts of Simulated Weightlessness by Dry Immersion on Optic Nerve Sheath Diameter and Cerebral Autoregulation. Front Physiol. 2017 Oct 12;8:780. doi: 10.3389/fphys.2017.00780. eCollection 2017.
citation: Navasiolava NM, Custaud MA, Tomilovskaya ES, Larina IM, Mano T, Gauquelin-Koch G, Gharib C, Kozlovskaya IB. Long-term dry immersion: review and prospects. Eur J Appl Physiol. 2011 Jul;111(7):1235-60. doi: 10.1007/s00421-010-1750-x. Epub 2010 Dec 14.