Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05641636 |
| Other study ID # |
A-3011 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 11, 2019 |
| Est. completion date |
October 28, 2022 |
Study information
| Verified date |
November 2022 |
| Source |
I.M. Sechenov First Moscow State Medical University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of research is to study to adverse cardiovascular disorder and risks factors in
childhood cranial and craniospinal tumors survivors. In this research the investigators
investigate cardiological instrumental diagnostic, such as electrocardiography,
echocardiography with the determination of global longitudinal strain, cardiopulmonary
exercise test, and diagnostic of endothelial function by Angioscan for the prediction of
cardiovascular complications after cranial and craniospinal radiotherapy and chemotherapy.
Description:
Cardiovascular disease, after recurrence of the original cancer and development of second
primary cancers, has been reported to be the leading cause of premature mortality among
long-term childhood cancer survivors. Childhood cancer survivors after chemotherapy and
radiotherapy for cranial and craniospinal tumors are at increased risk of transient ischemic
attack, ischemic stroke. The mechanisms of vascular damage are not well understood.
Preventive measures are not developed.
The purpose of my research is to study to adverse cardiovascular disorder and risks factors
in childhood cranial and craniospinal tumors survivors.
Cardiovascular risk factors monitoring and modification, development of nursing and follow-up
guides of adult patients may improve outcomes in these patients after treatment for cranial
and craniospinal tumors in childhood. Attempts to develop more individualized risk prediction
for cardiovascular disease may help refine surveillance and counseling in the future.
This was an open prospective observational study. 68 people were enrolled in the study: 48
childhood cancer survivals after complex management of cranial and craniospinal tumors formed
the main group, and 20 healthy people formed the control group.
Criteria of inclusion to the main group were: age 16-40 years, radiation and chemotherapy for
cranial and craniospinal tumors in childhood or adolescence, completion of the therapy at
least one year before enrollment, signed informed consent. There were three separate types of
informed consent - for adults, for minors and for their parents. Minors were signing informed
consent in the presence of their parents.
Criteria of inclusion to the control group for healthy volunteers were demographics
comparable to the main group.
Criteria of exclusion were: standard contraindications to exercise testing, anemia,
pregnancy, psychiatric disease, alcohol or drug abuse, active malignancy, acute infection.
The study has been approved by the local ethics committee. At baseline, all patients
underwent comprehensive evaluation including collection of medical history, complete physical
exam, 12-lead ECG, hormone and lipid blood tests, echocardiography (Echo-CG), cardiopulmonary
exercise testing (CPET) and pulse wave analysis. Additional carotid duplex scanning was
performed in patients after craniospinal radiation therapy.
Echocardiography Left ventricular (LV) systolic and diastolic function, cardiac chamber
volumes, valve function and systolic pulmonary artery pressure were evaluated using
conventional transthoracic 2D-echocardiography (Dimension/Vivid 7 PRO, General Electric
Medical System, Norway) according to current guidelines. Left ventricle (LV) end diastolic
volume (LVEDV), end systolic volume (LVESV) and ejection fraction (LVEF) were measured with
the modified Simpson method.
Cardiopulmonary exercise testing CPET was conducted on a treadmill (Intertrack 8100,
Schiller, Switzerland) with a breath-by-breath algorithm of gas exchange analysis (Cardiovit
CS-200 Ergo-Spiro, Schiller, Switzerland), using Bruce, modified Bruce or Naughton protocols
depending on the level of physical tolerance. The researchers evaluated VO2 peak (highest
oxygen uptake attained during exercise) and METs as its derivative, percentage from predicted
VO2 peak (based on age, sex, height, and weight), anaerobic threshold (AT, defined by the
V-slope method as the level of oxygen uptake at the moment of dislinear rise in minute
ventilation and CO2 output relative to VO2, reflecting the shift to anaerobic metabolism and
bicarbonate buffering of increased lactic acid), O2 pulse (VO2 peak/peak heart rate),
ventilatory equivalent for carbon dioxide (VE/VCO2 slope), end-tidal CO2 pressure at rest and
at peak exercise (PetCO2 rest and PetCO2 peak). Patient's effort was considered substantial
if the self-reported number using a 1-10 modified Borg scale was ≥ 7 points and respiratory
exchange ratio (RER, defined as VCO2/VO2 ratio) was ≥1.0.
Endothelial function assessment Pulse wave characteristics were obtained using finger
photopletysmography (PPG) (Angioscan-01, AngioScan-Electronics) from an infrared light
sensor. The amount of light transmitted to the finger directly depends on the alterations in
its blood flow. The signal obtained during PPG is displayed as a digital volume pulse (DVP)
waveform. This wave usually demonstrates two deflections: an early systolic peak (a),
reflecting a direct pressure wave propagation from the left ventricle to the finger, and the
diastolic peak (b), that reflects backward pressure wave propagation to the aorta. The time
between these two peaks (peak-to-peak time, PPT) is proportional to the subject's height. We
measured large artery stiffness index (SI, a ratio between the length of aorta calculated
automatically based on height to PPT), reflection index of small resistive arteries (RI,
calculated as b/a x 100%), augmentation index (AI, defined as the ratio between late and
early systolic pulse wave peaks, expressed as percent from the pulse pressure) and
augmentation index normalized for pulse rate of 75 beats per minute (AIp75%) with regard to
the fact that the heart rate has a major impact on the augmentation of pulse pressure.
Endothelial function was also evaluated using occlusion index and shear rate during
post-occlusive reactive hyperemia (PORH) representing the magnitude of limb reperfusion after
a brief period of brachial artery occlusion. The probe was performed in the morning hours in
supine position after 15 minutes of rest in a comfortable quiet warm environment according to
a standardized protocol on subject preparation (fasting state, restriction of
moderate-to-high physical activity, nicotine, alcohol, caffeine or other vasoactive drugs 24
hours before the probe).
Statistical analysis Microsoft Excel spreadsheet application was used for data storage and
preparation for future analysis. Statistical analysis was performed using Prism 9.2.0
software. Python software was applied for multiple logistic regression models. The continuous
data were expressed as a mean value (M) ± standard deviation (SD) with a 95% confidence
interval (CI). Categorical variables were presented in absolute numbers and percentage and
computed by using two-tailed Fischer's exact test. Normality of distribution for quantitative
variables was tested using Anderson-Darling test as the first step and using Student t-test
or Mann-Whitney U-test as the second step. Normality of distribution was initially evaluated
as well before correlation analysis with a Pearson coefficient for normal data and with a
Spearmen coefficient for non-normal data. Multiple regression models were performed
considering multiple testing of hypotheses. The results of the study were presented as
histograms with pairwise comparison of correlation matrices. P-value <0.05 was considered
significant.
