Effects of RIC on Cognitive Function and Blood Oxygen Levels in Unacclimatized Adult at High Altitude

Study Overview
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Brief Summary
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Several studies have shown cognitive impairment such as memory, perception and learning skill during ascent to high altitudes. However, few studies have directly investigated the effect of high altitudes exposure on attention-a high-level cognitive function. Remote ischemic conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, It has been proven to be an effective strategy for neuroprotection in ischemic stroke and chronic cerebral ischemia patients.

Detailed Description
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This study will provide insights into the preliminary proof of principle, safety, cognitive dysfunction and blood oxygen levels protective effects of RIC in Adults Exposing to High Altitude Conditions, and this data will provide parameters for future larger scale clinical trials if efficacious.

Official Title
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Effects of Remote Ischemic Conditioning on Cognitive Function and Blood Oxygen Levels in Unacclimatized Adult at High Altitude

Conditions
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Adult

Intervention / Treatment
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* Device: RIC
* Device: sham RIC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age was between 19 and 30 years. All participants should meet the criteria which included right-hand dominance, normal or corrected-to-normal vision. the RIC group volunteers have no history of intravascular thrombosis in the bilateral upper limbs; The high altitude participants move into the high-altitude environment within one month, and the low altitude volunteers have long-term life in low altitude areas. Exclusion Criteria: Severe hepatic or renal dysfunction Severe hemostatic disorder or severe coagulation dysfunction Any of the following cardiac disease - rheumatic mitral and or aortic stenosis, prosthetic heart valves, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, patent foramen ovale, left ventricular mural thrombus or valvular vegetation, congestive heart failure, bacterial endocarditis, or any other cardiovascular condition interfering with participation Serious, advanced, or terminal illnesses with anticipated life expectancy of less than one year Patient participating in a study involving other drug or device trial study 7. Patients with existing neurological or psychiatric disease that would confound the neurological or functional evaluations 8. Unlikely to be available for follow-up for 3 months 9. Contraindication for RIC - severe soft-tissue injury, fracture, or peripheral vascular disease in the upper limbs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Altitude RIC group<br>Thirty young healthy males from the altitude of 3700 meters will be allocated to the High Altitude RIC group. They will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 200 mmHg for five cycles of 5 min followed by 5 min of relaxation of the cuffs, performed twice a day for a total of 7 days. The treatment was carried out using an electric auto-control device (patent number ZL200820123637.X, China) | Device: RIC<br>* Adults allocated to the RIC group will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 200 mmHg over systolic blood pressure for five cycles of 5 min followed by 5 min of relaxation of the cuffs.<br>|
| Sham Comparator: High Altitude Sham group<br>Thirty young healthy males from the altitude of 3700 meters will be allocated to the High Altitude Sham group. They will undergo a sham RIC procedure during which bilateral arm cuffs are inflated to a pressure of 60 mmHg for five cycles of 5 min, followed by 5 min of relaxation of the cuffs, performed twice a day for a total of 7 days. | Device: sham RIC<br>* Adults allocated to the sham group will undergo a sham RIC procedure during which bilateral arm cuffs are inflated to a pressure of 60 mmHg for five cycles of 5 min, followed by 5 min of relaxation of the cuffs.<br>|
| Experimental: Low Altitude RIC group<br>Thirty young healthy males from the altitude of 42 meters will be allocated to the Low Altitude RIC group. They will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 200 mmHg for five cycles of 5 min followed by 5 min of relaxation of the cuffs, performed twice a day for a total of 7 days. The treatment was carried out using an electric auto-control device. | Device: RIC<br>* Adults allocated to the RIC group will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 200 mmHg over systolic blood pressure for five cycles of 5 min followed by 5 min of relaxation of the cuffs.<br>|
| Sham Comparator: Low Altitude Sham group<br>Thirty young healthy males from the altitude of 42 meters will be allocated to the Low Altitude Sham group. They will undergo a sham RIC procedure during which bilateral arm cuffs are inflated to a pressure of 60 mmHg for five cycles of 5 min, followed by 5 min of relaxation of the cuffs, performed twice a day for a total of 7 days. | Device: sham RIC<br>* Adults allocated to the sham group will undergo a sham RIC procedure during which bilateral arm cuffs are inflated to a pressure of 60 mmHg for five cycles of 5 min, followed by 5 min of relaxation of the cuffs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attentional network test | The computer software attentional network test (ANT) as described by Fan et al. in 2002 will be used to measuring the Orienting function, executive function and alerting function. | change from baseline (pre-RIC treatment) at 7days after RIC treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| basic fibroblast growth factor | basic fibroblast growth factor will be detected. Blood samples will be drawn from cubital vein to test these biomarkers. | change from baseline (pre-RIC treatment) at 7 days after RIC treatment | 
| platelet derived growth factor | platelet derived growth facto will be detected. Blood samples will be drawn from cubital vein to test these biomarkers. | change from baseline (pre-RIC treatment) at 7 days after RIC treatment | 
| vascular endothelial growth factor | vascular endothelial growth factor will be detected. Blood samples will be drawn from cubital vein to test these biomarkers. | change from baseline (pre-RIC treatment) at 7 days after RIC treatment | 
| the rate of Adverse event | Any adverse event will be reported and its relationship with the RIC intervention will be evaluated. | change from baseline (pre-RIC treatment) at 7 days after RIC treatment | 
| distal radial pulses | It is an aspect which can reflect the safety of remote ischemic conditioning | within 7 days after RIC treatment | 
| the number of erythema in the skin | It is an aspect which can reflect the safety of remote ischemic conditioning | within 7 days after RIC treatment | 
| the number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure | it is an aspect which can reflect the safety of remote ischemic conditioning | within 7 days after RIC treatment | 
| the number of patients with any other adverse events related to RIC intervention as determined by the principle investigator. | it is an aspect which can reflect the safety of remote ischemic conditioning | within 7 days after RIC treatment | 
| heart rate | the heart rate will be measured by automatic blood pressure monitor | change from baseline(pre-RIC treatment) at 7days after RIC treatment | 
| blood pressure | Both systolic, and diastolic pressure will be measured by automatic blood pressure monitor | change from baseline(pre-RIC treatment) at 7days after RIC treatment | 
| blood oxygen saturation (SaO2) | The portable oxygen saturation ward apparatus (Datex -Ohmeda, USA) will be used to monitor the blood oxygen saturation (SaO2) | change from baseline(pre-RIC treatment) at 7days after RIC treatment | 
| cerebral oxygen saturation(TOI) | The cerebral oxygen monitor (EGOS-600, Jiangsu China) will be used to monitor the cerebral oxygen saturation (TOI). | change from baseline(pre-RIC treatment) at 7days after RIC treatment | 
| The peak systolic blood flow velocity (PSV) of bilateral middle cerebral artery (MCA) | This is a indicator of hemodynamic data ,it is measured by Transcranial Doppler ((DWL Doppler-Box, German) according to applicational specifications and technical standards | change from baseline(pre-RIC treatment) at 7days after RIC treatment | 
| end-diastolic blood flow velocity (EDV) of bilateral middle cerebral artery (MCA) | This is a indicator of hemodynamic data ,it is measured by Transcranial Doppler ((DWL Doppler-Box, German) according to applicational specifications and technical standards | change from baseline(pre-RIC treatment) at 7days after RIC treatment | 
| the mean flow velocity (MFV) of the subjects' bilateral middle cerebral artery (MCA) | This is a indicator of hemodynamic data ,it is measured by Transcranial Doppler ((DWL Doppler-Box, German) according to applicational specifications and technical standards | change from baseline (pre-RIC treatment) at 7 days after RIC treatment | 
| pulse index (PI) of the subjects' bilateral middle cerebral artery (MCA) | This is a indicator of hemodynamic data ,it is measured by Transcranial Doppler ((DWL Doppler-Box, German) according to applicational specifications and technical standards | change from baseline (pre-RIC treatment) at 7 days after RIC treatment | 
| The degree of palpation of tenderness--visual analogue scale | The degree of palpation of tenderness is an aspect which can reflect the safety of remote ischemic conditioning. The pain was assessed with visual analogue scale ( VAS) | within 7 days after RIC treatment | 
| the number of patients with any other adverse events related to RIC intervention as determined by the principle investigator | it is an aspect which can reflect the safety of remote ischemic conditioning | within 7 days after RIC treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult, remote ischemic conditioning, high altitude condition, cognitive function, blood oxygen levels