Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05926453 |
| Other study ID # |
DS-00772 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 17, 2023 |
| Est. completion date |
June 1, 2029 |
Study information
| Verified date |
June 2023 |
| Source |
Diakonhjemmet Hospital |
| Contact |
Birgitte Nellemann, MD PhD |
| Phone |
+4722451540 |
| Email |
birgittenellemann[@]diakonsyk.no |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Spondyloarthritis is a chronic inflammatory joint disease that affects the spine and
sacroiliac joints. Most untreated patients eventually experience impaired mobility of the
spine, pain and reduced physical function. Exercise is a cornerstone in the treatment of
patients with spondylarthritis and it has been shown that high intensity exercise is just as
effective in reducing disease activity as immunosuppressive medication. Additionally,
patients with spondylarthritis have increased risk of cardiovascular disease both due to
traditionally risk factors (obesity, high blood pressure etc) but also due to chronic
inflammation. A maximal cardiopulmonary exercise test (CPET) is a measure of
cardiorespiratory fitness that can be used to show progression of the exercise and which also
is correlated to all-cause mortality and life expectancy.
The investigators will validate an indirect maximal CPET against the gold standard with
direct gas exchange measurements in patients with spondylarthritis. The indirect test is less
time consuming, requires less sophisticated equipment, has lesser requirements to test
personnel and facilities, and has less expenditures than the direct test. With a validated
indirect maximal CPET the test of cardiorespiratory fitness will be more accessible for
patients with spondylarthritis both in-hospital but also municipal.
Description:
Spondylarthritis (SpA) is a chronic inflammatory disease which affects sacroiliac joints,
spine and peripheral joints with an onset usually before the age of 45 years. The prevalence
is approximately 1.5% and correlated to the distribution of the genotype HLA-B27 in the
population. Most untreated patients eventually experience limited mobility of the spine,
pain, reduced physical function and fatigue. There is a considerable likelihood for
significantly impaired quality-of-life, morbidity and work disability. Exercise is a
cornerstone in the treatment of patients with SpA, and it has been shown that supervised high
intensity interval training has equally positive effect on disease activity as biological
immunomodulating treatment. The inflammatory joint diseases have a high prevalence of
comorbidities such as cardiovascular disease (CVD) driven by both traditional and
non-traditional risk factors. The CVDs are an important cause of premature mortality for
patients with inflammatory joint diseases including SpA.. Traditional CVD risk factors such
as obesity and lower levels of physical activity, coupled with non-traditional risk factors
such as systemic inflammation, are key causal factors.
Cardiorespiratory fitness is a strong predictor of all-cause mortality and life expectancy
also for patients with SpA, and improved cardiorespiratory fitness seems to reduce the risk
of cardiovascular disease in a quantitative manner. The gold standard for measurement of an
individual's cardiopulmonary fitness expressed as the peak oxygen consumption (VO2peak) is
considered as the direct gas exchange measurements during maximal exercise of large muscle
groups such as running, cycling, or swimming. However, the direct gas exchange measurement is
time-consuming and requires technical instrumentation and highly skilled personnel, and it is
therefore often more convenient to use estimates. For the maximal exercise test to measure
correct VO2peak levels or estimate correct physical fitness the participants must be willing
and capable of pushing themselves with the assistance of cheering from the technical
personnel otherwise the VO2peak will be underestimated. It is therefore evident that the
result of the performed test depends on the maximal effort being executed.
The modified Balke protocol is a protocol often used in maximal cardiopulmonary exercise
testing (CPET) on a treadmill. According to this protocol the workload is increased by
elevated inclination to a maximum of 15%. If the participant is capable of further increased
workload the speed of the treadmill is increased till exhaustion of the participant. With the
indirect test, VO2peak is estimated from the time to exhaustion (TTE), incline of the
treadmill and the speed of the treadmill. The indirect test requires a treadmill with
adjustable incline, heart rate monitor and a stopwatch. The direct VO2 measurement is
performed with breath-by-breath gas exchange measurement of inspiratory and expiratory air by
a Hans Rudolph mask and direct analysis using an ergospirometer system. The direct gas
measurements require expensive and sophisticated equipment as well as trained personnel to
perform the test, and this is not standard in many of the out-patient clinics. Thus, the
indirect test is cheaper and less time-consuming for the participant and the health personnel
making it a more accessible test of cardiorespiratory fitness than the directly measured gas
exchange. The indirect estimate of physical performance has, to our knowledge, not yet been
validated against the direct gas measurement using the modified Balke protocol in patients
with SpA.
Hypothesis and research question The investigators hypothesise that the estimated VO2peak
from the maximal CPET is well correlated to the VO2peak measured by direct gas measurements
in patients with SpA.
Tests Modified Balke protocol for maximal CPET All participants are asked not to eat for
2-hours prior to the test and to empty their bladder right before the start of measurements.
Ahead of the CPET, participants will be familiarised with treadmill walking with a warm-up of
5 minutes at a 1.5% incline. The output setting for the CPET is 4.5% incline and an estimated
output level (unfit woman 4.3 km*h-1; unfit man/normal woman 4.7 km*h-1; fit woman/normal man
5.3 km*h-1; fit man 5.3 km*h-1). The incline is increased with 2% every minute, when an
incline of 15% is reached the pace of the treadmill is increased with 0.3 km*h-1 every minute
while the inclination is kept constant (15%) until participant exhaustion. The test is
complete when the participants reach their exhaustion point and are unable to continue the
test despite verbal encouragement from the test technician. The protocol is terminated in
advance of exhaustion if the test technician observes abnormal and/or adverse test values or
the patient requests to stop. Borg RPE ≥ 18, VO2 plateau (two averaged 30-second consecutive
measures), age and gender specific reference values for respiratory exchange ratio, blood
lactate above age references and the maximal heart rate within 90% of the age-predicted
maximum (211-(0.64*age) are used to validate the CPET as a maximal CPET at test termination.
Participants who do not fulfil at least 2 of the 4 requirements will be excluded from
analyses.
Calculations
For the indirect estimates the maximal CPET data TTE, inclination, and speed is used for
calculations of VO2peak. There will use two equations for indirect calculations:
The ACSM equation:
VO2peak = (0.1 * speed (m*s-1) + (1.8 * speed(m*s-1) * inclination (%)) + 3.5
The HUNT3 equation:
Men: 24.24 + (0.599 * inclination) + (3.97 * speed) - (0.122 * body weight) - (0.126 * age)
Women: 17.21 + (0.582 * inclination) + (3.317 * speed) - (0.116 * body weight) - (0.099 *
age) The two formulas will be compared and validate these calculations against the direct
CPET and the non-exercise formula from Kondiskalkulatoren (World Fitness Level).
Measurements The CPET will be performed on a treadmill with 12-lead ECG and scaled by the
modified Borg RPE (6-20). Blood pressure is measured before test start (mmHg) and every other
minute throughout the test. Heart rate is measured continuously during the CPET and Borg RPE
is reported every minute. HRpeak is registered together with the time point of its
occurrence. Before the CPET height (m), body weight (kg) and circumference of hip (cm) and
waist (cm) are measured. Body composition is measured by bioelectrical impedance analysis
(BIA).
Pulmonary function will be assessed by spirometer according to guidelines, and forced
expiratory volume (FEV1 L), forced vital capacity (L) and peak expiratory flow (L/min) will
be recorded from three attempts at maximal expiratory flow volume loops. Maximal voluntary
ventilation (MVV, L/min) will be measured twice by breathing deeply and rapidly for 12
seconds. In cases of poor technique, MVV will be estimated as FEV1 * 37.5. Gas exchange is
measured through a Hans Rudolph two-way mask using a breath-by-breath gas analysing system.
VO2max is defined as the plateau VO2 of two 30-second samples and the VO2peak is defined as
the highest VO2 measured during the test.
Blood lactate concentration is measured in a small blood sample from the fingertip within 60
seconds of test completion to evaluate level of anaerobic processes. CRP is measured in a
small blood sample from the fingertip before the CPET for ASDAS calculations.
