Clinical trial NCT05043974: Integrative Study of Physiological Changes Induced by a 5-Day Dry Immersion on 20 Healthy Female Volunteers (DI5-Women)
Official title: Integrative Study of Physiological Changes Induced by a 5-Day Dry Immersion, Used as a Ground-based Model to Mimic Weightlessness: a Pilot Study on 20 Healthy Female Volunteers (DI5-Women Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Weightlessness
Weightlessness; Adverse Effect
Keywords: Simulated Microgravity
Weightlessness
Dry immersion
Supportlessness
Lead sponsor: Centre National d'Etudes Spatiales
Sponsor class: OTHER_GOV
Collaborators: name: European Space Agency
First posted: 2021-09-14
Enrollment: 20
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Dry immersion (DI) is a ground-based model of prolonged conditions of simulated microgravity. 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 study is to evaluate the physiological changes induced by 5 days of dry immersion in the female organism. The main physiological systems will be explored before, during and after the 5 days of immersion through a battery of specific tests and measurements. The results will be analyzed by scientists specializing in each field in order to better understand the dry immersion model, to compare its effects with those of the bedrest model and those of spaceflight. The clinical (adverse effects, comfort of subjects) and operational aspects are also part of the secondary objectives of the study.

Detailed description: 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. Ground-based experiments simulating the effects of weightlessness are used to better understand the mechanisms of physiological adaptation, design and validate the countermeasures. Dry immersion (DI) is a ground-based model of prolonged conditions of simulated microgravity, which has been mainly used in Russia. The past years however, the model has been implemented as well in Europe and expertise in conducting DI studies has been gained in particular in France where a few DI studies have been conducted in the MEDES Space Clinic in Toulouse for CNES (French Space Agency). 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. Furthermore, physiological changes have been reported in the neuromuscular, skeletal and sensorimotor systems, in fluid electrolyte regulation, in the cardiovascular system, metabolism, blood and immunity, respiration, and thermoregulation. Dry immersion provides a unique opportunity to study the physiological effects of the lack of a supporting structure for the body (a phenomenon called 'supportlessness'). As such, dry immersion is proposed to mimic actual spaceflight in terms of the monotonous environment, posture-motion limitations, hemodynamic changes and hypokinetic effects, support unloading, and decreased proprioceptive input. Immersion studies have so far only been conducted in men and a minority of studies using the bedrest model have included women. Likewise, few studies conducted to date have investigated gender differences in the astronaut population. The small number of female astronauts may be part of the reason why scientific data are lacking to draw valid conclusions about possible gender differences. However, if women currently constitute only about 10% of astronauts, women are and will be more and more represented in crews. Women now constitute 30% of American crews and NASA (US space agency) has announced gender parity for crews on future lunar missions. It is therefore essential to study the physiological changes induced by weightlessness in women, to compare them with those observed in men and to develop efficient countermeasures for preventing them. The main physiological systems will be explored before, during and after the 5 days of immersion through a battery of specific standardized tests and measurements. The objective of the study is to evaluate the physiological changes induced by 5 days of dry immersion in the female organism. The study conditions such as patient recruitment, nutrition, data collection, data management, reporting for adverse events are standardized. The results will be analyzed by scientists specializing in each field in order to better understand the dry immersion model, to compare its effects with those of the bedrest model and those of spaceflight. The clinical (adverse effects, comfort of subjects) and operational aspects are also part of the secondary objectives of the study.

Twenty healthy female subjects will participate in the study. There is no published data on dry immersion with female participation to help calculation the sample size. Moreover, female spaceflight and bedrest data are scarce, and do not provide any insight into inter-individual variability. This prolonged DI protocol in women is conceived as a pilot, descriptive, explorative study, as well as an operational and methodological study. Power-based calculation of the number of subjects is not directly applicable for such explorative studies. However, based on effect sizes obtained with previous DI studies in men, a total of 20 subjects was deemed necessary for this study.

Eligibility criteria: Inclusion Criteria:

* Healthy female 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 158cm and 180 cm,
* Regular menstrual cycles and cycles lasting between 20 and 35 days,
* Without oestroprogestative contraception (i.e., oral progestative contraception, IUDs, implants or absence of contraception are allowed),
* 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:

  * if age \< 35 years: 35 ml/min./kg \< VO2max \< 55 ml/min./kg,
  * if age \> 35 years: 30 ml/min./kg \< VO2max \< 55 ml/min./kg,
* Non active smokers,
* No alcohol, or drug addiction, and no medical treatment (with the exception of the aforementioned accepted means of contraception),
* 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, in particular,
* Symptomatic orthostatic hypotension whatever the decrease in blood pressure,
* 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,
* Abnormal result for lower limbs echo-doppler,
* 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),
* Women who have stopped breastfeeding within 2 months before the start of the study,
* Women who have undergone an abortion within 3 months before the start of the study,
* Irregular menstrual cycles or cycles lasting less than 20 days or more than 35 days,
* Oestroprogestative contraception,
* Recent implementation or change in hormonal contraceptive (in the last 6 months),
* Bone mineral density: T-score ≤ -1.5,
* Poor tolerance to blood sampling,
* Having given whole blood (more than 8ml/kg) in a period of 8 weeks or less before the start of the experiment, or having given whole blood more than 3 times in the past year,
* 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 her 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 4500 Euros within 12 months for being a research subject,
* Subject who cannot be contacted in case of emergency,

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) :

* Pregnant women (urine pregnancy test performed at the selection visit and on the day of arrival in the facility),
* Women during childbirth and breastfeeding mothers,
* 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: Change in orthostatic tolerance
timeFrame: At baseline and after five days of dry immersion
measure: Change in peak aerobic power (VO2max test)
timeFrame: At baseline and after five days of dry immersion
measure: Change in plasma volume
timeFrame: At baseline and after five days of dry immersion
measure: Change in fluid shift distribution towards the cephalic region
timeFrame: At baseline, the first day to quantify the short term effect and the fifth day of dry-immersion to quantify the long term effect of fluid shift
measure: Change in vascular endothelium integrity
timeFrame: At baseline and during the five days of the dry-immersion period
measure: Change in circadian rhythms of blood pressure
timeFrame: At baseline and during the five days of the dry-immersion period
measure: Change in lower limb veins functions
timeFrame: At baseline, after four days of dry-immersion and after one day of recovery
measure: Change in body fluid compartments by bioelectrical impedance analysis
timeFrame: Baseline and during five days of dry-immersion
measure: Change in muscle strength
timeFrame: At baseline and after five days of dry-immersion
measure: Change in muscle fatigue
timeFrame: At baseline and after five days of dry-immersion
measure: Change in muscle volume at calf level
timeFrame: At baseline and after five days of dry-immersion
measure: Change in contraction time
timeFrame: At baseline and after five days of dry-immersion
measure: Change in bone metabolism
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Changes in cartilage metabolism
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in Resting Metabolic Rate (RMR)
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in nitrogen balance
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in Body Composition measured by DEXA
timeFrame: At baseline and at the end of the 5 days of dry-immersion
measure: Change in glucose tolerance (Oral Glucose Tolerance Test)
timeFrame: At baseline and after 3 days of dry-immersion (to be comparable to a previous study on men)
measure: Change in Core temperature
timeFrame: At baseline and during the 5 days of dry immersion
measure: Change in height
timeFrame: At baseline, during and after the 5 days of dry immersion
measure: Change in mid cerebral artery (MCA) blood flow velocity
timeFrame: Before and after the 5 days of dry immersion
measure: Change in mood
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in psychological affects
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in psychological state: sleep quality
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in psychological state: mental health
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in psychological state: coping strategies
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in cerebral autoregulation
timeFrame: At baseline and after 5 days of dry-immersion
measure: Change in Intra Cranial Pressure (ICP)
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in optic nerve sheath diameter (ONSD) considered as an indirect marker for intracranial pressure (ICP) estimation.
timeFrame: At baseline, during and after 5 days of dry-immersion
measure: Change in the optic nerve fibers thickness.
timeFrame: At baseline and after five days of dry-immersion
measure: Change in intraocular pressure (IOP)
timeFrame: At baseline, during and after five days of dry-immersion
measure: Change in visual acuity
timeFrame: At baseline and after five days of dry-immersion
measure: Change in visual field
timeFrame: At baseline and after five days of dry-immersion
measure: Change in the anatomical characteristics of the eye (optical biometry)
timeFrame: At baseline and after five days of dry-immersion
measure: Change in the central corneal thickness
timeFrame: At baseline and after five days of dry-immersion
measure: Change in the retina by non-mydriatic fundus retinography
timeFrame: At baseline and after five days of dry-immersion
measure: Change in the cornea topography
timeFrame: At baseline and after five days of dry-immersion
measure: Change in cerebral structures and in venous circulation of the brain by MRI
timeFrame: At baseline and after five days of dry-immersion
measure: Change in walking balance
timeFrame: At baseline and after five days of dry-immersion
measure: Change in standing balance
timeFrame: At baseline and after five days of dry-immersion
measure: Change in motion sickness susceptibility
timeFrame: At baseline and after five days of dry-immersion
measure: Change in coagulation cascade
timeFrame: At baseline, during and after 5 days of dry immersion
Secondary outcomes:
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Medes-Imps
Study officials:
affiliation: MEDES - IMPS
name: Arnaud BECK, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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: Linossier MT, Amirova LE, Thomas M, Normand M, Bareille MP, Gauquelin-Koch G, Beck A, Costes-Salon MC, Bonneau C, Gharib C, Custaud MA, Vico L. Effects of short-term dry immersion on bone remodeling markers, insulin and adipokines. PLoS One. 2017 Aug 14;12(8):e0182970. doi: 10.1371/journal.pone.0182970. eCollection 2017.