Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT03679299 |
Other study ID # |
Pro00083372 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
October 10, 2018 |
Est. completion date |
June 30, 2024 |
Study information
Verified date |
May 2024 |
Source |
University of Alberta |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Although asthma is a disease of the airways, research is now showing that asthmatics are more
likely to develop cardiovascular disease (CVD) compared to non-asthmatics. Vascular
dysfunction is seen in people at high risk of CVD and has been linked to inflammation. During
an asthma attack, levels of inflammation in the whole body increase, which could potentially
explain why asthmatics are at increased risk of CVD. In the proposed study the investigators
will examine if asthma attacks lead to increased risk of CVD by evaluating inflammatory
levels and vascular function directly following asthma attacks, 2 days and 14 days after
discharge. The investigators will compare these results to non-asthmatics. The results from
this study will help us understand why asthmatics are at increased risk of CVD.
Description:
BACKGROUND & SCOPE: While asthma is generally considered to be a disease of the airways,
there are important systemic consequences which have predisposed people with asthma to become
more likely to die from cardiovascular (CV) disease compared to non-asthmatics. Additional CV
risks have been reported in people with severe asthma, and there is a relationship between
reductions in lung function and cardiac death. To date, little is known in regards to the
interaction between an asthma exacerbation and CV risk.
Brachial flow-mediated dilation (FMD) is used as a non-invasive tool to evaluate endothelial
function. Brachial FMD is impaired in people with coronary dysfunction, and has been shown to
predict future CV events better than traditional CV risk factors. People with asthma have
previously been shown to have impaired endothelial function compared to non-asthmatics, but
the underlying mechanism(s) are unclear. The aim of this study is to evaluate the endothelial
function in people with asthma directly following an asthma exacerbation, 2 days and 14 days
post-exacerbation, as well as non asthmatic controls.
Applanation tonometry is a non-invasive tool to evaluate arterial stiffness. It measure the
pulse wave velocity (PWV), which is an independent predictor of cardiovascular risk. People
with asthma have previously been shown to have increased arterial stiffness compared to
non-asthmatics, but hte underlying mechanism(s) are unclear. Arterial stiffness will be
evaluated in people with asthma directly following an asthma exacerbation, 2 days and 14 days
post-exacerbation, as well as non asthmatic controls. Arterial stiffness, together with
endothelial function will give information on the vascular function of the individuals.
Chronic systemic inflammation is an established risk factor and predictor of future CV
events, and levels of systemic inflammation has been shown to be increased in asthma and to
be are related to disease severity. While systemic inflammation can directly impair vascular
function, it is unknown how an asthma attack may affect vascular function and CV risk. Thus,
to gain better understanding of the increased CV risks associated with an asthma
exacerbation, this study will evaluate the level of systemic inflammation in people with
asthma directly following an asthma exacerbation, 2 days and 14 days post-exacerbation, as
well as non asthmatic controls.
OBJECTIVE 1: To examine the vascular function and systemic inflammation in young adults
experiencing a naturally occurring asthma exacerbation and to compare these data to values
obtained from two follow up visits, as well as to healthy controls.
METHODS & PROCEDURES: Outline:
Each participant from the exacerbation group will be tested at three different times: Day 1)
ED visit, Day 2) 48 hours post ED, Day 3) 14 days post ED.
A waist circumference measurement will be taken. Waist circumference will be measured at the
level of the last rib to the nearest 0.1 cm after a normal expiration.
On Day 1, participants will be recruited by the Emergency Medicine Research Group (EMeRG).
They will receive standard emergency care for their asthma and once stabilized, informed
consent will be obtained. Once stabilized, the participant will be taken to a private area
within the ED department to ensure no interference with ED procedures. Applanation tonometry
will be done to measure PWV, followed by brachial FMD to determine endothelial function and
lastly a blood sample will be obtained to measure serum CRP.
On Day 2 the participant will return and the same assessments as Day 1 will be performed with
the addition of spirometry. A FitBit will be given along with instructions to wear the device
for 7 days.
Day 3 will consist of the same measurements done in the ED for Day 1, with the addition of 2
quality of life questionnaires, the standardized Asthma Quality of Life Questionnaire (AQLQs)
and the EQ-5D (5L), and the Asthma Control Questionnaire (ACQ), finishing with a pulmonary
function test. Healthy controls will be tested two times, 48 hours apart. The same
assessments as the exacerbation group will be done, but no FitBit or questionnaires will be
given.
Spirometry: the participant will be tested for significant airway reversibility as per
established clinical guidelines
Pulmonary function: A standard pulmonary function test will be performed by all participants
as per established clinical guidelines.
Systemic inflammation and immune response markers present in venous blood samples will be
analyzed at the University of Alberta.
Vascular function: Flow-mediated dilation (FMD) of the brachial artery following 5 minutes of
forearm occlusion will be measured ultrasound imaging using our ultrasound machine. FMD will
be determined using Doppler ultrasound immediately after the release of the occlusion. The
secondary outcome is arterial stiffness, which will be determined using carotid - radial
pulse wave velocity, and PWV will be calculated from measurements of pulse transit time and
the distance traveled by the pulse between recording sites.
Physical Activity: will be measure with a FitBit activity monitored and calculated as average
steps/day.
Questionnaires: will asses asthma control, disease specific quality of life, and generalized
quality of life.
Data Analysis
The mean differences in FMD, systemic inflammation, and arterial stiffness for ED visit
compared to the control group will be evaluated using an unpaired t-test. A within-factors
repeated measures analysis of variance (ANOVA) will evaluate the mean differences between
each assessment day for the exacerbation group to assess change in endothelial function
during exacerbation as well as the recovery period. A similar evaluation will be used for
arterial stiffness and systemic inflammation. A one-way analysis of covariance (ANCOVA) will
be used to correct for shear rate in FMD for all groups, with both values being reported. A
Pearson correlation will be used to determine any relationship between recovery rate and
physical activity levels. In an exploratory sub analysis, unpaired t-tests will be used to
evaluate the sex differences for each outcome.
An α-level of 0.05 will be used as the significance level for all statistical analysis, and
all results will be reported as mean ± standard deviation unless indicated otherwise.While
the impact of asthma exacerbations on vascular function is currently unknown, sample size
calculations based on preliminary velocity-time integral (VTI) data from 11 confirmed
asthmatics who underwent mannitol and placebo challenges indicate a total of 36 asthmatics
and 36 controls would be sufficient to detect a 13% difference between these groups in VTI.
Our preliminary data show a large increase in CRP in asthmatics experiencing an exacerbation
vs. stable patients (7.3 vs. 0.5 mg/L, p<0.05), which would correspond to a substantial
increase in CV risk, and be detectable with this sample size. An additional 8 participants
per group will be recruited (i.e. 44 asthmatics and 44 controls) to compensate for potential
dropouts. Sub-analyses evaluating potential sex-based differences will be exploratory and
results will be considered hypothesis-generating.