Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05191979 |
| Other study ID # |
H-21011041 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 6, 2022 |
| Est. completion date |
November 1, 2025 |
Study information
| Verified date |
November 2023 |
| Source |
University of Copenhagen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The present project aims to investigate the interaction between training-induced blood volume
expansion (plasma- and red blood cell volume responses), central as well as peripheral
cardio-vascular adaptations. We will investigate cardiovascular responses through one year of
training in recreationally active men and women as well as endurance athletes undertaking
shorter training-periods/interventions with environmental heat-stress.
The overall purpose with the project is to investigate the physiological effects of prolonged
aerobic exercise on central cardiovascular parameters and peripheral effects in the muscle
tissue in untrained individuals. Further, we want to compare these effects to exposure to
environmental stress (heat) on performance well trained individuals. The present study
consist of three parts using the same methodology in different populations to elucidate the
above mentioned mechanisms. The first part is a larger training intervention in
untrained/recreationally active men and women aiming at evaluating the initial cardiovascular
adaptations to an exercise training regimen. In addition there are two parts aimed to
elucidate the mechanisms leading to further improvements in cardiovascular and blood volume
adaptations from exercise training in a different environmental condition and artificially
elevated PV in already highly adapted endurance athletes.
Description:
Background It is well established that a high maximal oxygen consumption (VO2max) is
associated with excellent physical performance in endurance sport disciplines. In order to
achieve a high V ̇O2max several things must be optimized as according to the Fick equation.
One of the main determinants of VO2max is the oxygen carrying capacity of the blood, which is
dictated by the total hemoglobin mass and is significantly higher in endurance athletes than
untrained individuals.
Naturally, this system is tightly regulated to maintain a steady blood composition and to
promptly recover blood volume if lost due to i.e. hemorrhage but can also be altered by
exercise and or exposure to extreme environmental conditions. Changes in blood volume and
composition can be seen already after two weeks of conventional exercise training where
increases in PV are seen in combination with elevated erythropoietin (EPO) while red blood
cell volume remains unaffected. This supports the proposed notion of the kidney acting as a
"critmeter" and that a reduced hematocrit due to expansion of PV thereby may regulate
erythropoiesis. In already trained individuals i.e. athletes, PV and Hbmass can be further
increased through repeated and or prolonged exposure to altitude or hot environmental
conditions.
Research questions and hypothesis
1. Explore gender and individual differences in the time course and relationship between
cardiovascular (central and peripheral) adaptations to long-term aerobic training and
the concomitant blood volume changes.
2. Evaluate differences between genders and factors influencing individual differences
(high vs. low responders) - hypothesizing that female have a blunted cardiovascular
response to long-term aerobic training.
3. What is the relative significance of blood volume, muscle metabolic and cardiovascular
adaptations for performance and aerobic power.
An incremental exercise test on a cycle ergometer will be conducted to determine the maximal
work rate and VO2max. Four venous blood samples, each 4 ml, is taken during the rest period.
Subjects blood volume and body composition are evaluated with a DXA-scan and CO-rebreathing
technique after a brief period of rest following the exercise test.
In the second experimental trials (visit 2), participants will be familiarized to the
experimental protocol by cycling in the semi-recumbent position. For the experiment
participants will undergo a standardized test of orthostatic tolerance by a lower-body
negative pressure (LBNP) of -15mmHg for maximally 10 min and -30mmHg for maximally 10 min.
Ventricular function are measured at both levels of LBNP. After the orthostatic tolerance
test the subject will perform semi-recumbent cycling at two submaximal intensities with
euhydration (control). At least 30 min after the first bout of exercise (after the subject
have returned to baseline hemodynamic levels), subjects will ingest a hypertonic beverage
with the aim of increasing PV by ~15% (intervention). Ventricular function is again measured
before the second bout of semi-recumbent submaximal cycling is initiated at the same
intensities as before mentioned.
In the third visit (visit 3) we will measure whether the exercise regimen have effects on
peripheral (arm) blood flow regulation. The peripheral vascular function is determined by
measures of brachial artery diameter and blood velocity using duplex ultrasonography before
and after flow-mediated dilation (FMD) where a cuff positioned around the upper arm is
inflated to 200 mmHg for 5 min for then to be deflated. Vascular sensitivity and endothelial
function is then measured by ultrasound before and after infusion of the vasoactive drugs
Acetylcholine (Ach) (25 and 100 μg min-1 (kg arm-mass)-1), Sodium Nitroprusside (SNP) (0.75,
1.5 and 3.0 μmol min-1 L arm-mass-1). Between all these measurements there will be a break of
minimum 15 min. Before the subject leaves this visit for the first time (baseline) two muscle
biopsy's of approximately 150 mg is also taken for cultivation of cells and assessment of
changes in capillary density, muscle fiber composition and mitochondrial density and
function. One muscle biopsy will also be taken during visit one at sampling point after 2
weeks, 1, 2 and 6 months after baseline and with two muscle biopsy's at 12 months after the
baseline round making for a total of eight biopsy's for each subject.
After the first round of experiment has concluded the subjects will undergo an exercise
regimen for 12 months, consisting of 3-4 supervised and monitored cycling training sessions
weekly. The exercise training will be supervised and structured in a progressive manner to
accustom the subjects to regular and high intensity exercise. Subjects will again undergo
study procedures at 2 weeks 1, 2, 6, and 12 months after baseline measures in order to allow
for continuous analysis of the short- and long-term cardiovascular adaptations. In addition
we want to measure coronary blood flow, muscle mitochondrial volume - and function to
determine the effects of central versus peripheral adaptations to long term training at
baseline, 2, 6 and 12 months.
In order to discern any central cardiovascular effects from peripheral we want to acutely
normalize blood volume by phlebotomy at the final visit of the 12 month exercise training.
Before and after phlebotomy, VO2max and Q̇max will be determined to investigate any central
cardiovascular adaptations.
Subjects in this project are subjected to the following measures: Cardiac and vascular
ultrasound, muscle biopsies, Catheterization with arterial and venous blood samples,
CO-rebreathing technique, DXA-scan, Electrocardiogram (ECG), Flow-mediated dilation,
vasodilator response to intra-arterial infusion of Ach and SNP, LBNP, performance test, and
Phlebotomy.
