A Randomized Controlled Study on 24 Healthy Male Volunteers Evaluating the Effects of Centrifugation and Exercise to Prevent the Deconditioning Induced by 60 Days of Head-down Bedrest Used as a Ground-based Model to Mimic Weightlessness.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Change in walking balance
研究概览
简要总结
The objective of this study is to investigate whether a cycling exercise coupled with artificial gravity via a short-arm human centrifuge helps to prevent and / or reduce the deleterious effects induced by 60 days of anti-orthostatic bedrest.
The secondary objective is to investigate whether the combination of a supine cycling exercise with artificial gravity is more effective than the same supine cycling exercise alone in preventing or reducing the effects of head-down bedrest.
During a randomized, 60 day bed rest study, in 24 healthy male adults, the two following aims will be undertaken:
- Fourteen scientific protocols will assess the changes in the cardiovascular, metabolic, musculoskeletal, neuro-sensorial, haematological, and immunological systems.
- In the above-mentioned systems, the comparative potential beneficial effects of the two countermeasure protocols will also be investigated by the scientific protocols and bedrest standard measurements (BSM).
详细描述
Space flights have shown the possibilities and limitations of human adaptation to space. For the last 60 years, results have shown 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 weightlessness can lead to significant loss of bone and muscle mass, strength, cardiovascular and sensory-motor deconditioning, immune, hormonal and metabolic changes .
Moreover, recently a new suite of physiological adaptations and consequences of space flight has been acknowledged. Indeed, after long flights, some astronauts present persistent ophthalmologic changes, mostly a hyperopic shift, an increase in optic nerve sheath diameter and occasionally a papillary oedema now defined by National Aeronautics and Space Administration (NASA) as Spaceflight-Associated Neuro-ocular Syndrome (SANS). Some of these vision changes remain unresolved for years post-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.
Overall, spaceflight induces physiological multi-system deconditioning which may impact astronauts' efficiency and create difficulties upon their return to normal gravity. Understanding the underlying mechanisms of these processes and developing efficient countermeasures to prevent, limit or reverse this deconditioning remain important challenges and major priorities for manned space programs.
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. 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 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. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
Participants and investigators are aware of the groups distribution
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male volunteer (see below the description of medical tests and laboratory analysis performed at the selection visit)
- •Aged 20 to 45 years
- •No overweight nor excessive thinness with BMI (weight kg/ height m2) between 20 and 27 kg/m2
- •Height between 158 and 190 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, of the ear, nose, throat (especially orthostatic hypotension and vestibular disorders), orthopaedic or musculoskeletal disorders
- •Good mental health: tests and psychological interview will be held by a specialist in extreme environment
- •Fitness level assessment: 35 mL/min/kg < VO2max < 55 mL/min/kg
- •Non active smokers
- •No alcohol or drug dependence, and no medical treatment
- •Covered by a Health Insurance System
- •Having signed the information consent
- •Free of any engagement during the study
排除标准
- •Any history or presence of clinically relevant cardiovascular, neurological or ear, nose, throat disease, 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 systolic blood pressure 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,
- •Vestibular disorders
- •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),
- •Bone mineral density: T-score ≤ -1.5,
- •Poor tolerance to blood sampling,
- •Having given whole blood (more than 7 mL/kg) in a period of 8 weeks or less before the start of the experiment, or having given whole blood more than 2 times in the past year,
- •Significant history of allergy, especially no dermatological or food allergy,
- •Significant anomaly detected in the biological analysis,
- •Positive reaction to any of the following tests: hepatitis A immunoglobulin, hepatitis B antigen, anti hepatitis C antibodies, anti Human Immunodeficiency Virus 1+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 4500 Euros within 12 months for being a research subject,
- •Subject who cannot be contacted in case of emergency,
- •Subject who had the two knees injured
- •MRI contraindications
- •History or active claustrophobia
- •Osteosynthesis material, presence of metallic implants or any other contra-indication for MRI
- •Vulnerable persons according to French law (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
- •Adults subject to legal protection (subject under guardianship or trusteeship) or unable to express their consent
研究组 & 干预措施
Control Group
Control group does not receive any countermeasure program during the head down tilt phase.
干预措施: Control Group (Behavioral)
Artificial Gravity and Supine Bike
The volunteers in this group receive countermeasure exercises during the head down tilt phase.
6 days over 7, they will perform a 30 minutes exercises on a supine bike (incremental steps) combined with artificial gravity generated with a short arm centrifuge.
干预措施: Countermeasure AG-Bike (Behavioral)
Supine Bike
The volunteers in this group receive countermeasure exercises during the head down tilt phase.
6 days over 7, they will perform a 30 minutes exercises on a supine bike (incremental steps).
干预措施: Countermeasure Supine Bike (Behavioral)
结局指标
主要结局
Change in walking balance
时间窗: At baseline and at recovery at week 10
Functional mobility test (such as sit and walk, heel to toe steps with eyes closed and open) will assess walking balance
Changes in orthostatic tolerance
时间窗: At baseline and first day of recovery
Orthostatic tolerance will be assessed during a tilt test combined with Lower Body Negative Pressure test (LBNP test)
Change in serum bone resorption markers
时间窗: From baseline until the end of the volunteers' participation in the study at year 2
Change in C-terminal cross-linked telopeptide of type I collagen (CTx, pmol/L) and N-terminal cross-linked telopeptide of type I collagen (NTX, pmol/L) will be assessed by chemiluminescence immunoassay.
Change in nitrogen balance
时间窗: At baseline and at recovery at week 12
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.
Changes in jump performance
时间窗: At baseline and at recovery at week 12
Jump performance will be assessed on a platform and height of the jump will be evaluated
Change in standing balance
时间窗: At baseline and at recovery at week 10
Standing balance will be assessed by posturography eyes open and eyes closed on a platform covered with 12-cm thick medium density foam
Change in mood
时间窗: At baseline and until week 12
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).
Changes in plasma volume
时间窗: At baseline and end of head down tilt phase at week 10
Plasma volume (L) will be assessed by the carbon monoxide-rebreathing method
Changes in leg muscle volume and fat
时间窗: At baseline and at recovery at week 10
MRI of the lower extremity will assess the degree of atrophy and changes in fat content in the musculature
Changes in bone density (by DEXA and High Resolution Peripheral Computed Tomography (HR-pQCT))
时间窗: From baseline until the end of the volunteers' participation in the study at year 2
Bone density is measured at lumbar and hip level with DEXA and at tibia and radius level with HR-pQCT
Change in visual field
时间窗: At baseline and at recovery at week 12
Visual field measured by standard automated perimetry
Changes in peak aerobic power (VO2max test)
时间窗: At baseline and end of head down tilt phase at week 10
Exercise capacity wil be assessed by graded cycling on sitting ergometer until exhaustion
Changes in serum bone formation markers
时间窗: From baseline until the end of the volunteers' participation in the study at year 2
Change in bone-specific Alkaline Phosphatase (bAP, µg/L) and procollagen type I N-terminal propeptide (P1NP, µg/L) will be assessed by chemiluminescence immunoassay
Changes in Resting Metabolic Rate (RMR)
时间窗: At baseline and at recovery at week 12
RMR will be measured by indirect calorimetry technique
Change in fat and lean body mass measured by dual energy x-ray absorptiometry (DEXA)
时间窗: From baseline until the end of the volunteers' participation in the study at year 2
Dual energy x-ray absorptiometry is a standard clinical technique to assess fat (g) and lean (g) body mass.
Change in intraocular pressure (IOP)
时间窗: At baseline and at recovery at week 12
IOP is measured with air tonometry
Change in muscle strength
时间窗: At baseline and at recovery at week 10
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
Change in the optic nerve fibers thickness
时间窗: At baseline and at recovery at week 12
Thickness of the optic nerve fibers will be measured by Optical Coherence Tomography (OCT)
Change in fluid shift distribution towards the cardiac and cephalic region
时间窗: At baseline and until year 1
The consequences of the fluid shift on the cardiac and cephalic area will be assessed by quantifying the right and left Jugular veins volumes (mL), as well as the left ventricle diastolic/systolic volumes (mL) by ultrasound.
Change in visual acuity
时间窗: At baseline and at recovery at week 12
Far and near visual acuity are tested uncorrected, or if applicable with own correction with digital acuity system
Change in the anatomical characteristics of the eye (optical biometry)
时间窗: At baseline and at recovery at week 12
Optical biometry measured by partial coherence interferometry
Change in the central corneal thickness
时间窗: At baseline and at recovery at week 12
Central corneal thickness on a single point on the cornea measured by Ultrasonic pachymetry
Change in the cornea topography
时间窗: At baseline and at recovery at week 12
Cornea topography measured by corneal topography equipment (like Pentacam). The elevation topography allows the mapping of the anterior and posterior surface of the cornea.
Change in motion sickness susceptibility
时间窗: At baseline and at recovery at week 12
Assessed by the Motion Sickness Susceptibility Questionnaire Short form (MSSQ-Short). MSSQ-Short scores possible range from minimum 0 to maximum 54, the maximum being unlikely. Higher scores means a higher motion sickness susceptibility
Change in sleep quality
时间窗: At baseline and until week 12
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 wake time. The following parameters are registered or assessed: Bedtime, wake time, 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.
Measurement of changes in subjective sleep quality
时间窗: At baseline and until week 12
Changes in subjective sleep quality will be measured using the Karolinska sleepiness scale (KSS) two times per day (bed time) every week.
Change in the retina by non-mydriatic fundus retinography
时间窗: At baseline and at recovery at week 12
Non-mydriatic fundus retinography allows a fundus photography to be taken and thus a color image of the papilla, retinal vessels and macula
Change in affective states
时间窗: At baseline and until week 12
Positive and Negative Schedule (PANAS) questionnaire will be used to assess the intensity of positive and negative affective states. PANAS self-report questionnaire consists of two 10-item scales to measure both positive and negative affects Each item is rated on a five-point Likert Scale, ranging from 1 = Not at all to 5 = Extremely, to measure the extent to which the affect has been experienced in a specified time frame. Positive affects: scores can range from 10 - 50 with higher scores representing higher levels of positive affect. Negative affects: scores can range from 10 - 50 with higher scores representing higher levels of negative affect.
Change in psychological state: mental health
时间窗: At baseline and until week 12
General Health Questionnaire-28 (GHQ-28) will be used to assess psychological 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
次要结局
- Change in pulse wave velocity in carotid and femoral arteries(At baseline and until year 1)
- Changes in myokinins.(At baseline and until week 12)
- Change in vertebral bone marrow fat fraction.(At baseline and until year 1)
- Changes in brain structure(At baseline and until week 12)