Understanding the Negative Effects of Bed Rest and Using Exercise as Countermeasure

Aging Clinical Trial

Official title:

Microgravity Research Analogue (MRA): Understanding the Health Impact of Inactivity for the Benefit of Older Adults and Astronauts Initiative

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04964999
• Other study ID #: MP-37-2021-7170
• Status: Recruiting
• Phase: N/A
• Start date: July 12, 2021
• Est. completion date: April 2022

Study information

• Verified date: September 2021
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: Guy Hajj Boutros
• Phone: 514-934-1934
• Email: guyelhajj[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Physical activity appears to be an important lifestyle habit to achieve healthy aging by promoting autonomy and quality of life. Interestingly, the dramatic changes that the human body undergoes due to bedrest for illnesses and hospitalization are similar to those seen over decades of normal aging. Bedrest in otherwise healthy older individuals can lead to a reduction of muscle size and strength, changes in bone strength and function of the heart and blood vessels. Bedrest can also lead to changes in keeping proper balance as well as changes in processing and understanding information. All of these factors negatively affect activities of daily living leading to physical function impairment and development of frailty, a clinical condition associated with an increased risk for disease and death.

The purpose of this study is to investigate whether exercise can counteract the negative effects of 2-week head tilt down bed rest on muscle function and metabolism, postural control, bone structure, orthostatic tolerance and cognitive function in adults.

For this study the investigators will recruit 24 healthy men and women between 55 - 65 years of age. All subjects will spend a total of 26 days (5 days of adaption period, 14 days of bed rest with 6 degrees of downward inclination, and 7 days of recovery period) at the McGill University Health Centre (MUHC). During this study, 12 subjects will randomly undergo an exercise intervention as countermeasure during the 14 days of bed rest period and 12 will serve as control.

Each subjects participation in this study will involve 1 telephone call (pre-screening) and 4 visits at the MUHC: 1 screening visit (Visit 1) followed by a 26-day long visit (Visit 2) and 2 follow-up visits (Visit 3 and Visit 4). During Visits 2 - 4 various measurements will be performed to assess sensorimotor control, muscle function and metabolism, bone structure, cardiovascular function, cognitive performance and function, and specimen collection (blood, urine, saliva, feces and muscle tissue).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: April 2022
• Est. primary completion date: February 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 65 Years

Eligibility

Inclusion Criteria:

• A minimum of 20 and a maximum of 24 non-smoking participants in the age group of 55 to 65 years old, half male and half female.

• Female participants must be menopausal (no menses for at least 1 year (or documented ovariectomy) and a serum FSH above 30 IU/L).

• Height between 158 to 190 cm with a body mass index between 20 to 30 kg/m2.

• Physically and mentally healthy subjects that will have successfully passed the psychological and medical screening appropriate for the age group.

• Participation in at least 2.5 hours of exercise at a moderate to vigorous-intensity aerobic activity per week.

• Willing to be assigned randomly either to the exercise or the control group.

Exclusion Criteria:

• Participants must be dementia-free, drug- or alcohol-addiction free, with no history of heart attacks, no thrombosis risk, no severe allergies, no hypocalcaemia, no uric acidemia, no orthostatic intolerance, no vestibular disorders, no considerable musculoskeletal issues, no chronic back pain, no head trauma, no seizures, no ulcers, no renal stones, no gastro-esophageal reflux disease or renal function disorder, no hiatus hernia, no migraines, and no mental illness.

• Electrocardiogram abnormalities

• Anemia

• Low bone mineral density

• Medication requirements that may interfere with the interpretation of the results

• Recent substandard nutritional status

• Claustrophobia

• Special dietary requests (e.g. vegetarian, vegan or some other diet)

• Sedentary people and people that are addicted to exercise

• Metallic implants (pacemakers, ICDs, CRT devices, infusion pumps, cerebral artery aneurysm clips, dental implants, tissue expander etc.), osteosynthesis material

• Given blood in the past 3 months before the onset of the experiment

• Smoked (tobacco and/or marijuana (THC)) within 6 months prior to the start of the study

• Abused drugs, medicine or alcohol within up to 30 days prior to the start of the study

• Participated in another study within 2 months before study onset

Related Conditions & MeSH terms

• Aging

Intervention

Other:
• Exercise
Participants will undergo an exercise program during the 2-week bed rest period.

Locations

Country	Name	City	State
Canada	Royal Victoria Hospital - Glen site	Montréal	Quebec

Sponsors (4)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre	Canadian Frailty Network, Canadian Institutes of Health Research (CIHR), Canadian Space Agency

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in cognition status of participants with head down bed rest (HDBR) with and without exercise countermeasure.	NIH Toolbox Cognition Battery (computerized)	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in cognition status of participants with head down bed rest (HDBR) with and without exercise countermeasure.	CLSA cognition questionnaire	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in emotional status of participants with HDBR with and without exercise countermeasure.	Positive and Negative Affect Scale; - For both scales scores can range from 10-50, with higher scores representing higher levels of positive or negative affect.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in emotional status of participants with HDBR with and without exercise countermeasure.	General Health Questionnaire (GHQ-28).; Using Likert 4-point scale with the min score being 0 and max score being 84.; Higher scores indicate a higher level of distress.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in brain structure with HDBR with and without exercise countermeasure.	Assessment of brain anatomy using a MRI.	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in brain function with HDBR with and without exercise countermeasure.	Measurement of neuronal, cerebrovascular, and connectivity integrity with functional MRI.	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in muscle muscle mass with HDBR with and without exercise countermeasure.	Body MRI	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in muscle fat infiltration with HDBR with and without exercise countermeasure.	Body MRI	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in adiposity with HDBR with and without exercise countermeasure.	Body MRI	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in ventricular volume of the heart with HDBR with and without exercise countermeasure.	Using a heart MRI left and right ventricular volumes will be assessed.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in ventricular mass with HDBR with and without exercise countermeasure.	Using a heart MRI left and right ventricular mass will be assessed.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in bone structure with HDBR with and without exercise countermeasure.	High resolution peripheral quantitative computed tomography (HR-pQCT)	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in muscle strength with HDBR with and without exercise countermeasure.	Quantitative Muscle Dynamometry (Biodex)	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in muscle strength with HDBR with and without exercise countermeasure.	Vertical jump	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in muscle-pump baroreflex with HDBR with and without exercise countermeasure.	Supine-to-stand test	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in balance control with HDBR with and without exercise countermeasure.	Postural equilibrium control test	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in orthostatic tolerance with HDBR with and without exercise countermeasure.	Tilt test	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Cardiac and vascular changes with HDBR with and without exercise countermeasure.	Using high frame rate ultrasound (HiFRUS) arterial wall shear stress will be assessed.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Cardiac and vascular changes with HDBR with and without exercise countermeasure.	Using high frame rate ultrasound (HiFRUS) arterial wall stiffness will be assessed.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Cardiac and vascular changes with HDBR with and without exercise countermeasure.	Using high frame rate ultrasound (HiFRUS) cardiac mass will be assessed.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Cardiac and vascular changes with HDBR with and without exercise countermeasure.	Using high frame rate ultrasound (HiFRUS) patterns of blood flow will be assessed.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in Fractional Synthesis Rate (FSR) with HDBR with and without exercise countermeasure.	Measurement of protein turnover.	Throughout the 26-day study period: during HDBR period
Primary	Changes in sleep quality with HDBR with and without exercise countermeasure.	Sleep quality will be assessed using a 3-electrode electroencephalogram (EEG) Sleep Profiler and a wrist worn actigraphy.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in sleep architecture with HDBR with and without exercise countermeasure.	Using 3-electrode electroencephalogram (EEG) Sleep Profiler electrical patterns of brain activity will be measured in order to assess sleep cycles and sleep stages.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in frailty status with HDBR with and without exercise countermeasure.	CLSA-FI questionnaire	Throughput the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in the gut microbiome with HDBR with and without exercise countermeasure.	To assess gut microbiome, stool samples will be collected and targeted sequencing of the variable regions 4 and 5 (V4-V5) of the 16S ribosomal RNA gene will be performed on an Illumina MiSeq.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in the constitution of the oral microbiome with HDBR with and without exercise countermeasure.	To assess oral microbiome, saliva samples will be collected and targeted sequencing of the variable regions 4 and 5 (V4-V5) of the 16S ribosomal RNA gene will be performed on an Illumina MiSeq.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Primary	Changes in physical performance with HDBR with and without exercise countermeasure.	Short Physical Performance Battery test	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in physical performance with HDBR with and without exercise countermeasure.	Timed-up-and-Go test	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in dynamic balance with HDBR with and without exercise countermeasure.	Four-square step test	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in bone markers with HDBR with and without exercise countermeasure.	The following bone markers will be assessed using ELISA kits: Total osteocalcin; Undercarboxylated osteocalcin; Sclerostin; NTX (N-terminal Telopeptide); CTX (C-terminal telopeptide); Bone Specific Alkaline Phosphatase (BSAP); Procollagen type 1 amino-terminal propeptide (P1NP)	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in growth factors with HDBR with and without exercise countermeasure.	The following growth factors will be measured with Multiplex: Basic fibroblast growth factor; Granulocyte colony-stimulating factor (G-CSF); Granulocyte-macrophage colony-stimulating factor (GM-CSF); Platelet-derived growth factor BB (PDGF-BB); Transforming growth factor ß (TGF-ß); Vascular endothelial growth factor (VEGF)	Throughout the 26-day study period: at Baseline and Recovery periods
Primary	Changes in cytokines with HDBR with and without exercise countermeasure.	The following cytokines will be measured with Multiplex: Eotaxin; Interferon gamma (IFN-?); IL-1ß, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17; Tumour necrosis factor (TNF-a); Interferon gamma- induced protein 10 (IP-10); Monocyte chemoattractant protein 1 (MCP-1); Macrophage inflammatory protein-1a (MIP-1a); Macrophage inflammatory protein-1ß (MIP-1ß)	Throughout the 26-day study period: at Baseline and Recovery periods
Secondary	Changes in neuromotor function with HDBR with and without exercise countermeasure.	Neuromuscular activity will be assessed using electromyography.	Throughout the 26-day study period: at Baseline and Recovery periods
Secondary	Changes in aerobic capacity with HDBR with and without exercise countermeasure.	Bicycle Ergometer Test	Throughout the 26-day study period: at Baseline and Recovery periods
Secondary	Changes in body composition with HDBR with and without exercise countermeasure.	Lean muscle and fat mass will be assess using dual energy X-ray absorptiometry.	Throughout the 26-day study period: at Baseline and Recovery periods
Secondary	Changes in insulin sensitivity with HDBR with and without exercise countermeasure.	Will measure excursion curves of glucose and insulin.	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Secondary	Changes in neuronal factors with HDBR with and without exercise countermeasure.	The following bone markers will be assessed using ELISA kits: Neurofilament light chain; Glial fibrillary acidic protein; Myelin basic protein; Total tau; Aß1-40; Aß1-42; BDNF	Throughout the 26-day study period: at Baseline, HDBR and Recovery periods