A 60 Days Head Down Tilt Bedrest With Artificial Gravity and Cycling Exercise on 24 Healthy Male (BRACE)
NCT Number: NCT06544213
Acronym: BRACE
Status: ACTIVE_NOT_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Simulated Microgravity by Head Down Tilt Bedrest|Weightlessness
Interventions: BEHAVIORAL: Control Group|BEHAVIORAL: Countermeasure Supine Bike|BEHAVIORAL: Countermeasure AG-Bike
Sponsor: Centre National d'Etudes Spatiales
Collaborators: European Space Agency|MEDES - IMPS
Sex: MALE
Age: ADULT
Enrollment: 24
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: BASIC_SCIENCE
Start Date: 2023-02-06
Completion Date: 2026-04-30
Locations: MEDES-Institut de Médecine et Physiologie Spatiale, Toulouse, 31400, France

Summary:
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).

Primary Outcome Measures: Changes in orthostatic tolerance, Orthostatic tolerance will be assessed during a tilt test combined with Lower Body Negative Pressure test (LBNP test), At baseline and first day of recovery|Changes in peak aerobic power (VO2max test), Exercise capacity wil be assessed by graded cycling on sitting ergometer until exhaustion, At baseline and end of head down tilt phase at week 10|Changes in plasma volume, Plasma volume (L) will be assessed by the carbon monoxide-rebreathing method, At baseline and end of head down tilt phase at week 10|Changes in serum bone formation markers, 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, From baseline until the end of the volunteers' participation in the study at year 2|Change in serum bone resorption markers, 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., From baseline until the end of the volunteers' participation in the study at year 2|Changes in Resting Metabolic Rate (RMR), RMR will be measured by indirect calorimetry technique, At baseline and at recovery at week 12|Change in nitrogen balance, 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., At baseline and at recovery at week 12|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 at recovery at week 10|Change in fat and lean body mass measured by dual energy x-ray absorptiometry (DEXA), Dual energy x-ray absorptiometry is a standard clinical technique to assess fat (g) and lean (g) body mass., From baseline until the end of the volunteers' participation in the study at year 2|Change in walking balance, Functional mobility test (such as sit and walk, heel to toe steps with eyes closed and open) will assess walking balance, At baseline and at recovery at week 10|Changes in jump performance, Jump performance will be assessed on a platform and height of the jump will be evaluated, At baseline and at recovery at week 12|Change in standing balance, Standing balance 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 recovery at week 10|Changes in leg muscle volume and fat, MRI of the lower extremity will assess the degree of atrophy and changes in fat content in the musculature, At baseline and at recovery at week 10|Changes in bone density (by DEXA and High Resolution Peripheral Computed Tomography (HR-pQCT)), Bone density is measured at lumbar and hip level with DEXA and at tibia and radius level with HR-pQCT, From baseline until the end of the volunteers' participation in the study at year 2|Change in the optic nerve fibers thickness, Thickness of the optic nerve fibers will be measured by Optical Coherence Tomography (OCT), At baseline and at recovery at week 12|Change in intraocular pressure (IOP), IOP is measured with air tonometry, At baseline and at recovery at week 12|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 at recovery at week 12|Change in visual field, Visual field measured by standard automated perimetry, At baseline and at recovery at week 12|Change in the anatomical characteristics of the eye (optical biometry), Optical biometry measured by partial coherence interferometry, At baseline and at recovery at week 12|Change in the central corneal thickness, Central corneal thickness on a single point on the cornea measured by Ultrasonic pachymetry, At baseline and at recovery at week 12|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 at recovery at week 12|Change in the cornea topography, Cornea topography measured by corneal topography equipment (like Pentacam). The elevation topography allows the mapping of the anterior and posterior surface of the cornea., At baseline and at recovery at week 12|Change in motion sickness susceptibility, 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, At baseline and at recovery at week 12|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 right and left Jugular veins volumes (mL), as well as the left ventricle diastolic/systolic volumes (mL) by ultrasound., At baseline and until year 1|Change in mood, 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)., At baseline and until week 12|Change in affective states, 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., At baseline and until week 12|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 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., At baseline and until week 12|Change in psychological state: mental health, 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, At baseline and until week 12|Measurement of changes in subjective sleep quality, Changes in subjective sleep quality will be measured using the Karolinska sleepiness scale (KSS) two times per day (bed time) every week., At baseline and until week 12
Secondary Outcome Measures: Change in vertebral bone marrow fat fraction., This will be performed by using MR scanning sequences that specifically measure water and fat signals then calculate the respective content., At baseline and until year 1|Changes in myokinins., Mass spectrometry will be performed on proteins obtained from muscle biopsies, microdialysis and serum. The generated peptides will be analysed using high resolution mass shot-gun mass spectrometry., At baseline and until week 12|Changes in brain structure, Both structural and functional brain changes associated with head-down bedrest will be examined by 3 Tesla MRI. Imaging sequence parameters will be selected to maximize sensitivity to effects of interest., At baseline and until week 12|Change in pulse wave velocity in carotid and femoral arteries, Change in pulse wave velocity in carotid and femoral arteries will be assessed by non-invasive ultrasound measurements., At baseline and until year 1