Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05710653 |
| Other study ID # |
UNAB-FCR-KINE2023A |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 28, 2022 |
| Est. completion date |
May 25, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Universidad Nacional Andres Bello |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background: Although exercise training is a well described therapy for some cardiometabolic
diseases such as obesity, type 2 diabetes, arterial hypertension, and metabolic syndrome,
there is scarcity of knowledge about the post-exercise period term as 'detraining' where
usually all physiological adaptations as cardiovascular and metabolic benefits are lost due
to physical inactivity. Likewise, as some exercise training modalities as high-intensity
interval training improve vascular parameters including endothelial dysfunction parameters as
flow-mediated dilation (FMD%), and carotid-intima media thickness (c-IMT) during the
'training' period, there is little knowledge about how many 'volume' or 'intensity' of
exercise training or physical activity per week is needed to maintain the exercise training
benefits in populations with cardiometabolic risk factors such as those patients with
arterial hypertension. This information will be of great interest for both improving and
maintaining the vascular profile and health of Chilean adults with risk factors and to
maintain a better vascular profile. Objective: To study the beneficial adaptations from the
'training' and 'detraining' period of exercise training on functional and structural vascular
parameters in healthy and cardiometabolic risk factors adult subjects to improve the health
profile. Methods: The investigators will conduct an experimental design of 5 groups of
exercise training in healthy (controls) and hypertensive (HTN) patients (≥140 mmHg), with
overweight/or obesity, men and women, with BMI ≥25 and ≤35 kg/m2, aged ≥18y, physically
inactive (<150 min/week of low/moderate PA/week, or <75 min/week of vigorous PA) in the last
6 months will be invited for participating. The groups will be as follows; Group (HTNex will
be compared with Group HTNcg). Group (ELEex will be compared with Group ELEcg). Group (NTex
will be compared with Group NTcg). Each group will be compared in their physiological
vascular adaptations before and after exercise training such as HIIT, and after 3 months of a
detraining period. Results (hypothesis): The investigators hypothesized that the maintenance
of vascular outcomes after the 'detraining' period is intensity-dependent in adults with HTN
that participated of an exercise intervention.
Description:
Endothelial dysfunction (EDys) is characterized as a phenotypic alteration in the endothelium
of the arteries, characterized by prothrombotic, pro-inflammatory, an imbalance between the
actions of vasodilators and vasoconstrictors, and small resistance vessels. Functionally, the
endothelium acquires a proinflammatory state, with prothrombic properties, and is commonly
associated with cardiovascular diseases, such as arterial hypertension (HTN, i.e., higher
SBP, DBP], coronary artery disease, chronic heart failure, peripheral artery disease,
atherosclerosis, type 2 diabetes mellitus (T2DM), and chronic renal failure. Clinically, a
decrease of 0.62% in the endothelial function, measured by flow-mediated dilation (FMD%), is
associated with an increase of +20 mmHg in systolic blood pressure (SBP). Functionally, EDys
is expressed by FMD%, pulse wave velocity (PWV), or the aortic augmentation index (AIx) of
the brachial artery, and Structurally EDys is expressed by the carotid-intima media thickness
(c-IMT) among others. Methodologically, both FMD% and c-IMT outcomes can be assessed by a) a
non-invasive ultrasound, and b) by other more invasive technics.
Part of the mechanism that explains the reduced vasodilator capacity in EDys includes
decreased nitric oxide (NO) production, increased oxidative stress (ROS), and a decrease in
the production of hyperpolarizing factors. At the molecular level, the up-regulation of
adhesion molecules, generation of macrophage chemoattractant peptide-1, and the production of
plasminogen activator inhibitor-1 participate also in the inflammatory response related to
the prothrombic state in EDys. Other molecular linked mechanisms include that angiotensin II
and endothelin-1, hypercholesterolemia, altered insulin signaling, and hyperglycemia can
contribute to EDys. Thus, EDys is a preliminary event before atherosclerosis, increasing
plaque accumulation, involving molecular pathophysiological events, but also 'functional' and
'structural' detectable damage, that are highly linked with cardiovascular disease (CVD).
In this sense, the 'elevated' BP, clinically known as prehypertension (preHTN), and the HTN
itself, represent an enormous public health issue, considering their high correlation with
stroke, coronary heart disease, heart failure, and above to Chile, where there is accelerated
aging of the population, where HTN is more common in older adults. The adult population with
HTN have several other co-morbidities such as overweight/obesity (~40%), T2DM, and
dyslipidemia (i.e. increased low-density lipids [LDL-c], decreased high-density lipids
[HDL-c], or increased triglycerides), but are transversely physically inactive ~40% (i.e., to
do not adhere to national and international physical activity/exercise training
recommendations of at least 150 min/of physical activity/exercise training per week by the
WHO guidelines).
Exercise training (ExT), a particular monitored modality of physical activity, can work by
previous knowledge, as a 'therapy' for decreasing BP in HTN patients and in those with EDys.
ExT is a planned, regulated, and guided physical activity modality, where participants can
obtain benefits according to a dose applied (i.e., intensity, volume, frequency per week,
density) and the profile (i.e., healthy, or seek with cardiometabolic diseases as HTN,
dyslipidemia, T2DM, or others, increase fitness performance, but at the same time improve
vascular and health markers such as FMD%, c-IMT, SBP/DBP, or MAP in HTN. ExT can include
endurance training (ET), consisting of continuum exercise usually practice at low to
'moderate' intensity (walking/run/cycling/rowing, etc.), resistance training (RT), involving
loads and external weights (dumbells, exercise machines with loads) with high impact on
muscle and bone mass, but also with cardiovascular benefits as decreasing BP, and the last
studied high-intensity interval training (HIIT) modality, which is a low-volume of briefs
high-intensity intervals (usually cycling, rowing, or running) interspersed with recovery
rest periods, and that show a time-efficient cardiometabolic health. All these three ExT
modes have been shown to improve functionally, and structurally the EDys, to reduce BP, and
improve several anthropometric, body composition, cardiovascular, metabolic, and physical
fitness parameters in HTN patients, being this recently corroborated by the American
Colleague of Sports Medicine.
Exercise training in Endothelial dysfunction: A relevant meta-analysis from Higashi et al.
revealed that moderate-intensity of ET, increases the nitric oxide availability, promoting
improvements in EDys markers in healthy subjects. A Long-term ET promote also regular
endothelium-dependent vasodilation, and these physiological stimuli have been associated with
lower blood pressure levels in HTN individuals. A very recently published article from
Pedralli et al., where after 8-weeks of three different Ext modalities as ET, RT, and CT the
authors showed a significant improvement in both BP and EDys markers in HTN patients.
However, the relevance of these findings contain several scientific and methodological
concerns to be considered and generalized such as a) there were no included the
time-efficient exercise modality of HIIT, b) the investigators only reported FMD%, but not
other of relevance to the endothelial function as c-IMT, c) there were no different
frequencies groups of ExT/week, d) RT group worked at intensities ≥60% until 80% of the
maximum strength in patients, the baseline PA level was reported by questionnaires rather
than objectively measure PA using accelerometers devices, e) there was no diet control hour
before the BP and EDys measurements, and more importantly, there was no control group and
included both PreHTN, and HTN participants, among others (reported only results in 'mean',
but not inter-individual response to know responders (Rs) and non-responders (NRs) to ExT
modes. Additionally, and as a major concern, although there are some evidence that show
significant improvements of vascular parameters from exercise training such as FMD% and c-IMT
during the exercise-intervention periods, there is no evidence about how to maintain these
physiological vascular benefits during 'detraining', where there is scarcity of studies with
evidence about potential loss of these vascular adaptations, nor proposals of other minimum
exercise-dose to maintain these vascular adaptations during the post-exercise cessation
period.
Acute and long-term exercise training effects in BP and EDys markers: A single session of
endurance training (ET) reduces resting blood pressure 5-7 mmHg among HTN patients, and this
effect is sustained for up to 24h. This phenomenon is termed post-exercise hypotension
effect. Ciolac et al. showed that 40 minutes of ET at 60% of the heart rate reserve,
decreased SBP, and DBP day, and night, by using Holter monitors. Interestingly, the authors
showed that there was an increase in the sample of HTN patients who showed normal daytime SBP
(68% vs. 82), and nighttime diastolic blood pressure (56% vs. 72%). In HTN patients, after 60
minutes of ET (45 min, at 70% maximum oxygen consumption [VO2max]), Taylor-Tolbert et al.
reduced SBP -7.4, and DBP -3.6 mmHg, maintaining up to 24h the PEHE. After an acute session
of 60 minutes of ET, other authors had reported decreases in SBP -9.9 and DBP -6.2 mmHg in
healthy Chilean adults. Cade et al. in 1984 reported that ET normalized BP, and decreased
medications dosage in HTN patients after 12-weeks of training by decreasing SBP ~22, and DBP
~18 mmHg. However, after four decades of science and technological advances, there is wide
evidence from different ExT modalities as ET, HIIT, or RT, in favor of normalizing
(functionally) BP in HTN patients. Olea et al. have shown recently that after 24 sessions of
HIT ExT, there was a reduction from 145 to 118 mmHg SBP in the HTN group, where the healthy
normotensive group does not elicit changes. Interestingly, the authors reported a reduction
of -3.9 kg of body fat, and from the 100% of the HTN sample (n=22), at the final of the ExT
program, there was a 73% of patients that normalized (i.e., in the normotensive state) their
SBP. Chen et al. reported that HTN patients decreased SBP -15, and DBP -4 mmHg after 12
months of 4-courses of sports. Previously, at long-term ExT on BP changes, our team have
reported that long-term exercise training (≥4-weeks of regular exercise) in HTN patients
decrease SBP -20, and DBP -9 mmHg BP after concurrent training (CT) of combining both HIT
plus RT), decreasing SBP from 143 to 126 mmHg, and DBP from 83 to 71 mmHg in HTN patients.
Other investigators have shown that 16-weeks of HIIT in PreHTN patients decrease SBP -8, DBP
-5.8 mmHg, and healthy normotensive do not elicit changes. Interesting in this study, PreHTN
patients decreased also -3.3 kg weight, -3 cm waist circumference, -5.8% body fat, -13.9
mg/dL triglycerides, increase +5.0 mg/dL HDL-c, increase +3 kg muscle strength in lower
limbs, and improved their walking capacity by decreasing time in the 2 km walking test -3.1
min. After 12-weeks of ExT, other investigators reported significant decreases in PreHTN
patients at SBP from RT -4 and HIT -6 mmHg, and in DBP -3 mmHg in HIT, wherein both ExT
modalities reported significant improvements in obesity and physical fitness outcomes.
However, after 20-weeks of ExT using CT (ET plus RT), HTN, and PreHTN patients can change
their baseline diagnosis to another better stage, such as from HTN to PreHTN, or from PreHTN
to normotension. These relevant and significant changes were accomplished by significant
decreases in obesity, metabolic, and physical fitness markers. However, it was also reported
that there was a wide IVET, where around ~30%, 50%, and 20% of patients in the CT exercise
group showed no changes for improving body composition, blood pressure, and lipid profile,
being named as nonresponders. Thus it is imperative to study more the ExT effects, such as
HIIT and their physiological adaptations on EDys markers, and BP response in subjects with
cardiometabolic risk factors such as those adults with preHTN, or HTN, but above the study of
these parameters after a 'detraining' period and explore potential exercise dose to maintain
the beneficial vascular adaptations and thus to protect the vascular system and overall
health.
SARS Cov-2, Co-Morbidities and Exercise Training: The SARS Cov-2 viruses (COVID-19) have
globally damage the overall physical and mental health in all the worldwide population.
Unfortunately, although there are some asymptomatic subjects to the viruses, the main part of
the death attributable to the COVID-19 virus are those with major co-morbidities such as
population with obesity, HTN, cardiometabolic diseases and other with major respiratory
diseases. Unfortunately, COVID-19 pandemic state have included a high physical inactivity
situation that exacerbate the sedentary state and promote more impairment in blood pressure,
and vasculature. Particularly, EDys is impaired in COVID-19, where the impairment of
endothelial function have been related with more mortality risk in adults.
RESEARCH PROBLEM: Although there is relevant information about the ExT and their effects and
mechanisms on EDys markers improvements such as at FMD% and c-IMT, there is little
information regarding how long ExT in terms of 'volume' and 'intensity' can be able to
maintain these ExT improvements after exercise cessation in a 'detraining' period testing a
'moderate', or a 'low' exercise dose of 'high' and 'low' exercise-intensity. This information
could be useful for a decision to several ExT public health programs to the population with
cardiometabolic risk factors for CVD, as well as to improve future more complex studies for
predicting exercise response.
