Strength Training in Hypoxia to Improve Bone and Cardiovascular Health of Elderly
Phase: NA
Conditions: Aging Well
Sponsor: University of Extremadura

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Title: Strength Training in Hypoxia to Improve Bone and 
Cardiovascular Health of Elderly 
 
NCT number: not yet assigned 
 
Document Date: 25/May/2019 
 
 
 

 
 
 
 
 
 
 
Brief Summary 
 
Due to age-related effects, the bone and cardiovascular health are damaged. Physical 
exercise and in particular the strength training has been proposed as a fundamental tool 
to these pathologies, especially in the elderly. On the other hand, the use of normobaric 
hypoxia combined with exercise could have a beneficial synergistic effect on disease 
prevention and the quality of life of the elderly.  
Therefore, the general objective of this project is to analyze the effects of different 
methods of strength training combined with conditions of normobaric hypoxia on the 
bone and cardiovascular health of the elderly. This general objective is specified in the 
following specific objectives: 
- 
To analyze the effects of resistance circuit training on bone mineral density and 
bone remodelling markers of elderly, under normoxic and normobaric hypoxic 
conditions.  
- 
To analyze the effects of resistance circuit training on biochemical parameters, 
inflammatory, endothelial and clinical markers just like cardiovascular risk level of 
elderly, under normoxic and normobaric hypoxic conditions.  
- 
To analyze the effects of resistance circuit training on body composition and 
functional capacity of elderly, under normoxic and normobaric hypoxic conditions.  
- 
To analyze the effects of whole-body vibration training on bone mineral density 
and bone remodelling markers of elderly, under normoxic and normobaric hypoxic 
conditions.  
- 
To analyze the effects of whole-body vibration training on biochemical 
parameters, inflammatory, endothelial and clinical markers just like cardiovascular risk 
level of elderly, under normoxic and normobaric hypoxic conditions.  
- 
To analyze the effects of whole-body vibration training on body composition 
and functional capacity of elderly, under normoxic and normobaric hypoxic conditions.  
- 
To compare the effects of resistance circuit versus whole-body vibration training 
on bone and cardiovascular health of elderly, under normoxic and normobaric hypoxic 
conditions. 
- 
To value the normobaric hypoxic environment efficacy on bone and 
cardiovascular health of elderly subjected to resistance circuit and whole-body vibration 
training.   
 
We hypothesize that bone and cardiovascular health will improve in the participants 
subjected to both resistance training, but greater improved may be found when these 
protocol are combined with normobaric hypoxia.   
 

 
 
 
 
 
 
 
Methodology 
Participants 
Various associations of pensioners will be contacted as well as the university of seniors 
of the University of Extremadura to recruit volunteer participants. Total sample size will 
be 120 people, being this calculated to obtaining a statistical power of 90%, calculated 
with a margin of error of 5% and a mean difference of 10% in the study variables.  
Inclusion criteria will be: (1) women and men aged 65 years or older; (2) no current 
medical condition not compatible with planned exercise; (3) free of illness or 
medication potentially affecting the bone and cardiovascular system; (4) estimated daily 
calcium intake of 1200-2000 mg/day; (5) consumption of no more than two alcoholic 
beverages per day. Exclusion criteria will be: (1) participation in any other type of 
intervention based on physical exercise in the last 6 months in order to avoid 
interactions with the previous practice; (2) subjects have been above 1500 m during the 
last 3 months; (3) contra indications for whole-body vibration training: severe 
cardiovascular diseases, ocular diseases that affect the retina, neuromuscular and heart 
diseases, stroke, implant, bypass, stent, arthritis and other joint disease or epilepsy. 
Participants will be assigned to 6 different groups: (1) Normoxia Control Group 
(NCON), who will be instructed to continue with their normal daily activities for the 
entire duration of the study; (2) Hypoxia Control Group (HCON); who will perform an 
intellectual activity while they will be exposed to normobaric hypoxic conditions 
(16.0% FiO2); (3) Normoxia Circuit Training (NCIR); who will perform a circuit 
training with elastic bands in normoxic conditions (20.9% FiO2); (4) Hypoxia Circuit 
Training (HCIR); who will perform a circuit training with elastic bands in hypoxic 
conditions (16.0% FiO2); (5) Normoxia Vibration (NVIB); who will perform whole-
body vibration training in normoxic conditions (20.9% FiO2); (6) Hypoxia Vibration 
(HVIB); who will perform whole-body vibration training in hypoxic conditions (16.0% 
FiO2).  
All procedures will be performed in studies involving human participants will be in 
accordance with the 1964 Helsinki declaration and its later amendments or comparable 
ethical standards and the study design was approved by the Bioethical and Biosecurity 
Commission of the University of Extremadura (65/2018). 
  
Design 
This will be a randomised double-blind controlled study. There were separate 
intervention and assessment teams. We will try to blind the study for participants, as 
they will be trained/tested separately. Training sessions will be supervised by an 
experienced member of the research group. 
All interventions will be performed during 24 weeks, with a frequency training of 3 
days per weeks; sessions will be scheduled with at least one day of rest in between for 
optimal recovery. All patients were assessed at two time points: at baseline before the 
24 weeks of intervention (Pre)  and reassessed 7 days after the last session (Post). 
Participants will be instructed to continue with their normal daily activities, diet and 
caloric and calicium intake for the entire duration of the study.  
 
Interventions 
During several times of the session in each intervention, oxygen saturation (SpO2) will 
be controlled using a finger pulse-oximeter (Konica Minolta, Japan) and heart rate (HR) 

 
 
 
 
 
 
 
using a heart rate monitor (Polar team 2, Polar, Finland) to know the physiological 
challenge posed on the participants during the exposure. 
 
Passive hypoxia 
During 30 minutes of session, the participants will be performed an intellectual activity 
while they will be exposed to normobaric hypoxic conditions in a hypoxic chamber 
(CAT 310, Lousiville, Colorado). They will inspire oxygen fraction (FiO2) set to 16.1% 
(0.16) in order to simulate an altitude of 2500m above sea level.  
 
Normoxia circuit training 
Each training sessions will consist of a circuit training with elastic bands, where 
different muscle groups will be involved (pectoral, shoulders, back, arms, thighs, legs 
and abdominals). Duration of the session will be about 30 minutes, which will include 
10 minutes warm-up consisting of slight movements, and 5 minutes of static stretching 
for the muscles at the end of the sessions. Main section of the sessions will be a circuit 
that will be composed by 3 sets of 12-15 repetitions of nine different exercises. Six 
exercises will be performed using elastic resistance bands (ERS; TheraBand®): chest 
press, row, glute kickbacks, front and side raises, standing bíceps curls and tríceps 
kickbacks. To provide resistance with ERB, elastic bands with resistance ranging from 
light to very heavy loading (colors: yellow-gold) were used. ERBs were 2 meters, but 
the actual length used (grip on ERBs and distance to anchor point) was fine tuned for 
each subject in each exercise to find the correct resistance. When necessary to increase 
loading, two or more bands were combined. Bands were prestretched and never 
elongated more than 300% of resting length, as recommended by the manufacturer. 
Two additional exercise will be developed with kettlebell (KB): squat with 6 kg or 
increase loading until 10 kg; and hip trust, increase loading with support of a foot alone 
or with additional loading (KB of 5 or 10 kg). Finally, the subjects will keep a plank 
position during 15-20 seconds.     
Training will take place in a hypoxia chamber (CAT 310, Lousiville, Colorado, United 
States) will place in the laboratory. In order to blind subjects to altitude, the system will 
be run with normoxic airflow into the chamber (up to 1000 l/min) and will produce the 
same audible noise as in the hypoxic condition. Subjects will inspire FiO2 of 21.0% 
(0.21) to simulate an altitude of 459 m above sea level. Furthermore, all systems will be 
covered with fabric to prevent participants from visually identifying the normoxic or 
hypoxic conditions. FiO2 will be controlled regularly with an electronic device 
(HANDIC,Maxtec, Salt Lake City, Utah, United States). 
 
Hypoxia circuit training 
Each training sessions will consist of a circuit training with elastic bands, where 
different muscle groups will be involved (pectoral, shoulders, back, arms, thighs, legs 
and abdominals). Duration of the session will be about 30 minutes, which will include 
10 minutes warm-up consisting of slight movements, and 5 minutes of static stretching 
for the muscles at the end of the sessions. Main section of the sessions will be a circuit, 
that will be composed by 3 sets of 12-15 repetitions of nine different exercises. Six 
exercises will be performed using elastic resistance bands (ERS; TheraBand®): chest 
press, row, glute kickbacks, front and side raises, standing bíceps curls and tríceps 
kickbacks. To provide resistance with ERB, elastic bands with resistance ranging from 
light to very heavy loading (colors: yellow-gold) were used. ERBs were 2 meters, but 

 
 
 
 
 
 
 
the actual length used (grip on ERBs and distance to anchor point) was fine tuned for 
each subject in each exercise to find the correct resistance. When necessary to increase 
loading, two or more bands were combined. Bands were prestretched and never 
elongated more than 300% of resting length, as recommended by the manufacturer. 
Two additional exercise will be developed with kettlebell (KB): squat with 6 kg or 
increase loading until 10 kg; and hip trust, increase loading with support of a foot alone 
or with additional loading (KB of 5 or 10 kg). Finally, the subjects will keep a plank 
position during 15-20 seconds 
Training will take place in a hypoxia chamber (CAT 310, Lousiville, Colorado, United 
States) will place in the laboratory. Participants will inspire a fraction of inspired 
oxygen (FiO2) of 16.1% (0.16) to simulate an altitude of 2500 m above sea level; FiO2 
will be controlled regularly with an electronic device (HANDIC,Maxtec, Salt Lake 
City, Utah, United States).  
 
Normoxia whole-body vibration 
The subjects will perform dynamic and static vibration exercise provide by a 
commercially available device (Galileo 2000, Novotec GmbH, Pforzheim, Alemania). 
The duration of the WBV session will be about 30 minutes, which will include 10 
minutes warm-up consisting of slight movements, and 5 minutes of static stretching for 
the muscles at the end of the session.  
Repetitions of 30 seconds with a frequency of 18.5 Hz will be performed. The rest 
interval will be 60 seconds between 4 repetitions during weeks 1–12 and 45 seconds 
between 5 repetitions during weeks 12–24. The vertical amplitude of WBV was set at 
2.5 mm. Four stance will be performance, with the soles of both feet remained in 
contact with the platform: 
1) Stand with feet side-by-side on the board, which produced lateral oscillations of the 
whole body. During the vibration training sessions, the subjects will be barefoot to 
eliminate any damping of the vibration caused by footwear. The angle of flexion of the 
knees during the vibration exercise will be set at 60°.  
2) Begin with the feet placed perpendicular to the midline axis of the platform, with a 
foot positioned slightly ahead of the other foot. Lift the toes of the one foot and the heel 
of the other foot 4 mm above the surface of the platform. Bend the knees and maintain a 
45°knee angle. Keep the back and head straight. Alternate legs. 
3) Front foot 4 mm above the surface of the platform and back foot on ground, front 
knee angle 90°. Alternate legs 
4) Lay down on the ground, with the knees bent and feet flat on the platform. Keep the 
arms at your side with your palms down. Lift the hips off the ground until the knees, 
hips and shoulders form a straight line. Hold your bridged position. 
Training will take place in a hypoxia chamber (CAT 310, Lousiville, Colorado, United 
States) will place in the laboratory. In order to blind subjects to altitude, the system will 
be run with normoxic airflow into the chamber (up to 1000 l/min) and will produce the 
same audible noise as in the hypoxic condition. Subjects will inspire FiO2 of 21.0% 
(0.21) to simulate an altitude of 459 m above sea level. Furthermore, all systems will be 
covered with fabric to prevent participants from visually identifying the normoxic or 
hypoxic conditions. FiO2 will be controlled regularly with an electronic device 
(HANDIC,Maxtec, Salt Lake City, Utah, United States).  
 
 

 
 
 
 
 
 
 
Hypoxia whole-body vibration 
The subjects will perform dynamic and static vibration exercise provide by a 
commercially available device (Galileo 2000, Novotec GmbH, Pforzheim, Alemania). 
The duration of the WBV session will be about 30 minutes, which will include 10 
minutes warm-up consisting of slight movements, and 5 minutes of static stretching for 
the muscles at the end of the session. 
Repetitions of 30 seconds with a frequency of 18.5 Hz will be performed. The rest 
interval will be 60 seconds between 4 repetitions during weeks 1–12 and 45 seconds 
between 5 repetitions during weeks 12–24. The vertical amplitude of WBV was set at 
2.5 mm. Four stance will be performance, with the soles of both feet remained in 
contact with the platform: 
1) Stand with feet side-by-side on the board, which produced lateral oscillations of the 
whole body. During the vibration training sessions, the subjects will be barefoot to 
eliminate any damping of the vibration caused by footwear. The angle of flexion of the 
knees during the vibration exercise will be set at 60°.  
2) Begin with the feet placed perpendicular to the midline axis of the platform, with a 
foot positioned slightly ahead of the other foot. Lift the toes of the one-foot and the heel 
of the other foot 4 mm above the surface of the platform. Bend the knees and maintain a 
45°knee angle. Keep the back and head straight. Alternate legs. 
3) Front foot 4 mm above the surface of the platform and back foot on ground, front 
knee angle 90°. Alternate legs 
4) Lay down on the ground, with the knees bent and feet flat on the platform. Keep the 
arms at your side with your palms down. Lift the hips off the ground until the knees, 
hips and shoulders form a straight line. Hold your bridged position. 
Training will take place in a hypoxia chamber (CAT 310, Lousiville, Colorado, United 
States) will place in the laboratory. Participants will inspire a fraction of inspired 
oxygen (FiO2) of 16.1% (0.16) to simulate an altitude of 2500 m above sea level; FiO2 
will be controlled regularly with an electronic device (HANDIC,Maxtec, Salt Lake 
City, Utah, United States).  
 
Outcome Measures 
Socio-Demographic Data and Lifestyle Questionnaires 
A general questionnaire was administered to collect medical and demographic data to 
check the inclusion/exclusion criteria. As control variables, prior and after the 
intervention, calcium intake was estimated using a food frequency questionnaire. The 
bone-specific physical activity questionnaire (B-PAQ) was used to assess the physical 
activity level of the participants in the last 12 months. 
 
Life Quality and Risk of Fall Questionnaires 
SF-36 questionnaire will be used to know the life quality. Risk of fall will be evaluated 
through Fall Efficacy Scale-International (FES-I). 
 
Cardiovascular Evaluation 
Clinical tests of cardiovascular evaluation, such as recording of blood pressure with 
sphygmomanometer, arm-ankle index and pulse wave velocity using ultrasound 
Doppler technique will be used. 
 
 

 
 
 
 
 
 
 
Cardiovascular Risk 
Cardiovascular risk will be determined based on the following factors: age, sex, 
smoking, total cholesterol, HDL cholesterol, systolic blood pressure and diabetes, as 
described in the FRESCO study. 
 
Anthropometric Measurements 
Weight, height, body mass index and waist-hip ratio will measure following standart 
procedures. 
 
Body composition 
Body composition variables such as percentage fat, lean and bone mass will be obtain 
using dual-energy X-ray absorptiometry (DXA,Norland Excell Plus; Norland Inc., Fort 
Atkinson, United States) of whole body and corporal segment. 
 
Bone Mineral Density 
Bone mineral content (g) and density (g/cm-2) and T-score of whole body and proximal 
femur region will be calculated from obtained data of dual-energy X-ray absorptiometry 
(DXA,Norland Excell Plus; Norland Inc., Fort Atkinson, United States) 
 
Blood Biomarkers 
Standard biochemical analysis (HDL, LDL and Total Cholesterol, Triglycerides and 
Glucose) will be obtained of blood samples, through a clinical chemistry analyzer 
(Spotchem, Arkray Factory, Germany). Bone remodelling (VEGF and SDF-1), 
inflammatory (C-reactive protein, IL-2, IL-4, IL-6 and TNF alfa) and endothelial 
(ICAM-1 and VCAM-1) markers will be analyzed by ELISA technique. 
 
Functional Capacity 
Senior Fitness Test battery will be used to know of physical condition of elderly: lower 
limb strength (Chair stand), upper limb strength (Arm curl), lower limb flexibility 
(Chair sit and reach), upper limb flexibility (Back scratch), endurance (6 min. walk) and 
agility (8ft Up and Go) will be tested through this battery. Furthermore, core muscle 
strength (plank test), grip strength (hand grip) and balance (single leg stance test) will 
be measured 
 

 
 
 
 
 
 
 
Statistical Analysis Plan (SAP) 
Statistical analyses will be performed using the statistical analysis package SPSS v.20 
(IBM, New York, United States). Data will be expressed as median and standard 
deviation.  Kolmogorov–Smirnov tests will be conducted to show the distribution of the 
studied variables and Levene’s test for homogeneity of variance. Repeated measure 
ANOVA will be used to compare the response of each variable, considering the sex and 
age as covariate. The p < 0.05 criterion was used for establishing statistical significance. 
Effect size (Cohen, 1992) will be also calculated for all variables, considering the 
magnitude of change as small (0.2), moderate (0.5) or large (0.8).  

 
 
 
 
 
 
 
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