The Efficacy of Normobaric Oxygen on Chronic Cerebral Ischemia
Phase: NA
Conditions: Normobaric Oxygen, Cerebral Ischemia
Sponsor: Capital Medical University

Official title: The efficacy of normobaric oxygen on chronic cerebral ischemia
NCT number: NCT03745092 (http://www.clinicaltrials.gov)
Date: December 1, 2018
Study protocol
Objective
The aim of this study was to investigate whether the normobaric oxygen (NBO) could
correct the chronic cerebral ischemia (CCI) induced EEG anomalies.
Design and methods
This was a prospective randomized cohort study and had been approved by the
Institutional Ethic Committee of Xuanwu Hospital, Capital Medical University
(Beijing, China) in accordance with the guidelines of the 1964 Declaration of Helsinki.
Informed consent was obtained from all individuals before collecting any data. From
December 2018 through December 2019, the patients who diagnosed as intracranial
arterial stenosis or internal carotid arterial stenosis in Xuanwu Hospital, Capital
Medical University and Beijing Fengtai You’anmen Hospital were enrolled in this
study with random number table. The diagnosis of intracranial arterial stenosis and
internal carotid arterial stenosis was confirmed by magnetic resonance angiography
(MRA) and/or computed tomographic angiography (CTA). All of the enrolled subjects
should comply with the following inclusion and exclusion criteria.

Inclusion criteria: (1) age from 18 to 80 years; (2) diagnosis of ICAS and/or ECAS;
(3) NIHSS≤4 and mRS≤2; (4) signed informed consent.
Exclusion criteria: (1) brain infarction occurring within recent two months; (2)
intracranial arterial aneurysm, dissection or malformation; (3) history of cerebral
hemorrhage or subarachnoid hemorrhage; (4) history of cerebral trauma; (5) history of
other brain injury or disorders; (6) austere diseases such as cancer, heart failure,
respiratory failures; (7) respiratory diseases; (8) poor compliance.
The participants underwent 30-minute EEG recording two times. Between the two
time recordings, they were randomly performed with NBO (received oxygen
supplement with 8L/min, via Venturi mask, maintaining 45min) and rest (had a rest
like lying, sitting or walking for 45min), which were labeled NBO group and control
group in this study.
The EEG recording was conducted with an EEG recording equipment (EEG YAL
PN-NET, Beijing Yunshen Science and Technology Corporation). Ag/AgCl electrodes
were positioned at Fp1, Fp2, F3, F4, F7, F8, Fz, C3, C4, Cz, P3, P4, Pz, T3, T4, T5,
T6, O1, O2, A1, A2 (21 channels) according to the international 10-20 system, with
electrode impedances all less than 5kΩ. The sampling rate was 256 Hz for all
channels using a 16 bit AD convertor. Channel A1 and A2 were as references. Five
minutes of artefact-free data was selected from EEG recordings in each subjects at
random, and these participants should maintain awake and lying quietly with eyes
closed as much as possible. Data filtering (band pass, 1 to 30Hz) was performed in
EEGLAB (version 2019.1) with supplementary scripts operating in the MATLAB

environment. The artefact removal (blink artefact and electromyogram artefact) was
performed again automatically using BSS algorithm (sobi) that was implemented into
EEGLAB software packages.
The absolute power (AP, with units uV2) was computed using Fast Fourier
Transform (FFT) for each electrode over the delta (1-4 Hz), theta (4-8 Hz), alpha
(8-13 Hz) and beta (13-20 Hz) frequency bands, and the relative power (RP) was a
ratio of the frequency band of interest power to the total power across the 1-20Hz
range. The power spectral density (PSD) for each channels was estimated via Welch’s
procedure with a 2-s Hamming window length. Besides over all channels,
fronto-central electrodes (F3, F4, Fz, C3, C4, Cz) which were with mild occipital
alpha oscillation impact, were also used to reflect the actual frequency activities in the
forehead. Proceeded by python software, the EEG wavelet entropy was calculated via
nonlinear dynamics method in order to evaluate the complex of brain function.34
Power ratio index (PRI) was defined as AP ratios of theta/alpha (TAR), delta/alpha
(DAR), (delta+theta)/(alpha+beta) (DTABR), and fronto-central alpha/occipital alpha
(FOAR) in this study. Each frequency band AP and RP reduction rate was calculated
as a ratio of pre-intervention minus post-intervention bandpower to pre-intervention
bandpower.
Statistical analysis
R software (http://www.r-project.org) was used for analysis in this study. The
continuous data was expressed as mean±standard deviation (SD) or median

(interquartile range, IQR). Dataset following a Gaussian distribution was analyzed
with Student’s t test; otherwise analyzed with Mann-Whitney U test. As for multiple
comparisons among groups, LSD method was used to remove the statistical bias from
repeated measure. The comparison between the prior to and post-intervention was
performed with paired samples t test and Wilcoxon test. Categorical data was
presented as num. (percentage) and proceeded by chi-square test. Multiple analysis
using linear regression model was to rule out the confounding effect of other
covariates that may affect the EEG measures. p-value <0.05 was indicative of
statistical significance.