Effects of Exercise Training as a Non-pharmacological Treatment for Metabolic Syndrome and Its Interactions With Subjects Habitual Medications.
Phase: EARLY_PHASE1
Conditions: Exercise Therapy, Metabolic Syndrome X, Cardiorespiratory Fitness
Sponsor: University of Castilla-La Mancha

1 
STUDY TITLE: 
INTERACTIONS BETWEEN PHYSICAL TRAINING AND 
MEDICATION IN PATIENTS WITH METABOLIC SYNDROME 
STUDY PROTOCOL 30 AUGUST, 2017

2 
METHODS 
PRE-POST research project with one ARM (group) and 2 evaluations in each of the 
times in a cross-over randomized fashion. 
Recruitment strategy 
Participants in this research will be recruited through advertisements in the local media 
(newspapers and radio), through which overweight volunteers will be requested 
according to body mass index (BMI <25). From this large pool of potential participants 
who respond to the advertisements, 40 sedentary men and women ages 25-65 who 
meet criteria for metabolic syndrome will be recruited. 
Inclusion and exclusion criteria 
The metabolic syndrome will be defined according to the presence of three of the 
criteria published by the International Diabetes Federation: waist circumference> 94 cm 
for men and> 80 for women of Caucasian ethnicity, high blood pressure figures (> 130 
mmHg for systolic and> 85 for diastolic), high fasting blood glucose (> 100 mg / dl) or 
dyslipidemia: (triglycerides> 150 mg / dl, HDL <40 mg / dl) (1). Participants must be in 
treatment with ARA II hypotensive drugs. All subjects must be physically inactive, at 
least during the previous year according to the criteria of the American College of 
Sports Medicine-ACSM (less than 150 min / week of moderate physical activity or less 
than 75 min / week of vigorous physical activity). 
In addition, participants must not have a diagnosis of any endocrine pathology other 
than carbohydrate intolerance and their hormonal levels (except insulin) must be within 
clinical normal ranges. Other exclusion criteria will be, recent surgery, cardiovascular 
disease (especially uncontrolled coronary disease, heart valve disease, heart failure, 
complex ventricular arrhythmias), diseases with kidney, liver, respiratory or 
neuromuscular involvement. Participants will be informed verbally and in writing of the 
risks and benefits regarding participation in the study and will provide their written 
consent. Participants will be supervised by their family doctors throughout the study. 
Intervention with physical training 
The training program will consist of 3 weekly sessions of interval aerobic exercise 
(EIA). EIA will consist of a cycle ergometer workout (or treadmill running) that includes 
a 10-minute warm-up period at 70% of the peak heart rate (HRpeak) followed by 5 
intervals of vigorous exercise of 4 minutes at 90-95% of your HRpeak interspersed with 
periods of 3 minutes of active recovery at 70% of HRpeak, ending with a 10-minute 
cooldown, reaching a total of 55 min duration per workout. Considering the effects of 
the circadian rhythm on the heart rate, the workouts will be carried out at the same time 
of day and the load will be adjusted daily to provoke the indicated heart rate. Because 
of the adaptations produced by exercise, the training load must be adjusted to reach 
similar heart rates over time and thus comply with the principle of overload for physical 
training. 
Nutritional control 
During the week prior to the start of the interventions, all participants will keep a written 
record of their morning weight (completely naked) and of all food consumed with their 
respective weights. Total energy and macronutrient intake will be evaluated through the 
individual record of each participant using software adapted to the eating habits of 
Spaniards (CESNID Nutritional Calculation Program V 1.0 - Center d'Ensenyament 
Superior de Nutrició I Dietètica assigned to the a University of Barcelona). With these 
data, the usual caloric intake will be established that will be maintained during the 4 
months of intervention to avoid biases due to weight loss resulting from a hypocaloric 

3 
Ejercicio 
o     
Reposo 
Seguimiento durante 3 horas 
Compo 
sición 
corpor 
al 
Presión Arterial 
Gasto Cardiaco 
Presión Arterial 
Gasto Cardiaco 
Presión Arterial 
Gasto Cardiaco 
PORH 
Onda de Pulso 
Presión Arterial 
Gasto Cardiaco 
PORH 
Onda de Pulso 
diet that would confuse the effects of the training program. 
Evaluation procedure 
Participants will go to the laboratory in the morning after an overnight fast and with or 
without their medication depending on the test. In each one the following 
measurements will be made: 
Figure 1. Diagram of the measurements of each of the test. 
8:00 
9:00 
10:00 
12:00
13:00 
Description of the variables to be measured 
Anthropometric measurements and blood pressure at rest 
Weight and height will be evaluated using a standard scale and a stadiometer that 
allows measuring with a precision of 0.1 cm and kg respectively (Seca, Vogel & 
Halke Hamburg, Germany). The body mass index (BMI; in kg / m2) will be calculated 
using the subject's height and weight. The waist circumference (in the horizontal 
plane 2 centimeters below the rib edge (1)) will be measured using a plastic 
measuring tape with a precision of 0.1 cm. 
To measure blood pressure, participants will be seated in a supine position for 15 
min. The systolic (SBP) and diastolic (DBP) blood pressure will then be determined 
with the help of an ambulatory pressure monitor (SunTec Medical, Oscar, USA). The 
average of the last 2-3 measurements will be used as the value of the SBP and DBP. 
Blood pressure during exercise 
During the exercise we will use a specific pressure meter for this situation that not 
only has a very sensitive microphone in the pressure cuff but is also integrated with 
the ECG monitoring through three leads (SunTec Medical, Tango, USA). We will use 
cuffs adjusted to the size of the participant's arm. 

4 
Post-occlusive reactive hyperemia (PORH). 
After 15 minutes of supine rest, participants will have a flush meter placed on the 
skin of the forearm (MoorLab, UK). This flowmeter is simply an adhesive probe that 
with laser technology measures the speed at which the red cells pass through the 
capillary circulation. Once the signal is good, a pressure cuff will be inflated on the 
arm 10 mmHg above the resting systolic pressure. The cuff will remain inflated for 3 
minutes. After this period of circulatory arrest, the pressure cuff will be opened, and 
the flow rate will be measured for 2 minutes. This is a measure of the ability of the 
peripheral vasculature to dilate upon a short-lived ischemic stimulus. 
Pulse wave 
Pulse wave velocity will be measured as an indirect measure of arterial stiffness. For 
this, a tonometer () placed manually in the carotid and femoral arteries will be used 
after having measured the distance between them and with reference to the xyloid 
process. It will be measured sequentially, using the R wave of the electrocardiogram 
as a reference to synchronize the signals. The time interval is measured at the 
beginning of the same, since these points correspond to the beginning of the 
ejection where the possibility of reflections is considered null, the delay being due 
only to the propagation of the wave. 
Blood chemistry analysis 
After a 15-minute supine position and prior to performing the exercise, 10 ml of 
venous blood will be drawn for the analysis of metabolic syndrome factors in blood.  
Thus, plasma glucose, insulin, triglycerides, total cholesterol and HDL-cholesterol 
will be measured.