The Impact of Serial Remote Ischemic Conditioning on Dynamic Cerebral Autoregulation in Healthy Adults
Phase: NA
Conditions: Remote Ischemic Conditioning
Sponsor: The First Hospital of Jilin University

 
 
 
 
 
 
The Impact of Serial Remote Ischemic Conditioning on Dynamic 
Cerebral Autoregulation in Healthy Adults 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The First Hospital of Jilin University 
NCT 04899362 
April 10th, 2021 
 
 

Background 
Remote ischemic conditioning (RIC) refers to an intervention that offers remote tissues 
and organs a resistance capacity to ischemia/reperfusion injury through small doses of 
reversible episodes of ischemia and reperfusion that activate neurogenic pathways, 
humoral factors, and the immune system. Recent studies have demonstrated that RIC 
could increase cerebral perfusion, promote hematoma resolution, facilitate recovery of 
nerve function, and improve the clinical prognosis of patients with cerebrovascular 
diseases. However, the mechanism is not fully elucidated. Our previous study found 
that dynamic cerebral autoregulation (dCA), an important indicator of cerebrovascular 
function which related to the prognosis of cerebrovascular disease, was improved after 
once round of RIC; however, the exact effect of serial RIC on dCA was unclear. 
Additionally, the dCA alteration period after serial RIC remains unknown. Solving 
these problems will help us to formulate detailed strategies for the safe and effective 
application of RIC in patients with cerebrovascular disease. 
Hence, the objective of this study was to observe the exact impact of serial RIC on 
dCA. This included determining when dCA was increased during serial RIC and the 
duration of the effect of serial RIC.  
 
Eligibility Criteria 
Inclusion Criteria: 
⚫ age from 18 to 50, both genders 
⚫ willing to participate in follow-up visits 
Exclusion Criteria: 
⚫ current or having a history of chronic physical diseases or mental diseases 
⚫ suffering from infectious diseases in late one month 
⚫ pregnant and lactating women 
⚫ smoking or drinking 
⚫ inability to cooperate sufficiently to complete the dCA examination 
 

Arms and Interventions 
Experimental: RIC group 
RIC was induced by 4 cycles of extremities ischemia (5-minute blood-pressure cuff 
inflation to 200 mm Hg, followed by 5-minute cuff deflation).All subjects will take 14 
RIC intervention, blood collection and 10 dCA measurements. 
Device: BB-RIC-D1/LAPUL Medical Devices Co, Ltd, China 
The RIC consisted of 4 cycles of extremities ischemia (5-minute blood pressure cuff 
inflation to 200 mm Hg, followed by 5-minute cuff deflation). The tourniquets were 
applied to one side upper arm. This intervention was undertaken twice a day for 7 days. 
Procedure/Surgery: Intravenous blood collection 
Nurses will collect intravenous blood 3ml four times (at baseline and the first, seventh 
and eighth day of the study). The blood samples will be stored for laboratory test.The 
blood samples only use for the trial. 
Device: dCA measurement 
Serial measurements of dCA were performed at 10 days, baseline, 1st, 2ed, 4th, 7th, 
8th, 10th, 14th, 21th and 35th of the study.The continuous ABP was measured non-
invasively using a servo-controlled plethysmograph (Finometer Pro, the Netherlands) 
at the middle finger. Two 2 MHz transcranial Doppler probe was used to measure 
continuous cerebral blood flow velocity (CBFV) simultaneously in the bilateral middle 
cerebral arteries at a depth of 45-60 mm Endtidal CO2 was monitored using a 
capnograph (MultiDop X2, DWL, Sipplingen, Germany). The probes were placed over 
temporal windows and fixed with a customized head frame. CBFV and continuous 
arterial blood pressure were recorded simultaneously from each subject in the supine 
position for 10 minutes. All data were recorded for further assessment and analysis. 
 
Outcome Measures 
Primary Outcome Measure: 
Dynamic Cerebral Autoregulation Parameter: Phase Difference(PD) in Degree   
[Time Frame: 36 days] 

Low PD at a low frequency band indicates impairment of autoregulation, as it suggests 
that cerebral blood flow velocity follows the changes in arterial blood pressure with a 
short delay. 
 
Secondary Outcome Measures: 
Dynamic Cerebral Autoregulation Parameter: Gain in cm/s/mmHg   [Time Frame: 36 
days] 
High gain at the same frequency band is also considered an indicator of compromised 
autoregulation for passively transferring the amplitude of arterial blood pressure to 
cerebral blood flow velocity. 
 
Statistical Analysis Plan 
The data were analyzed using the Statistical Program for Social Sciences version 26.0 
(SPSS; IBM, West Grove, PA). The distribution of data was assessed using a one-
sample Kolmogorov–Smirnov test. Normally distributed continuous variables are 
shown as mean±standard deviation, and non-normally distributed data are presented as 
the median and interquartile range. Repeated measurement analysis of variance was 
used to test the differences in the observed dCA values on different days. Two general 
linear models were used for the repeated measurements. To observe when dCA was 
increased during serial RIC, dCA parameters at baseline, d1, d2, d4, and d7 were 
included. To assess the duration of the effect of serial RIC, baseline, d7, d8, d10, d14, 
d21, and d35 were included. To compare the difference between the baseline and other 
days, a paired t-test was used. The changes in blood biomarker levels were analyzed by 
Friedman test. Baseline, d1 and d7, and baseline, d7 and d8 were compared respectively. 
A two-tailed p-value < 0.05 was considered statistically significant.