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

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

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.

Study Overview

• Status: Unknown
• Conditions: Adult
• Intervention / Treatment: Device: RIC; Device: sham RIC

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lian Duan, MD PHD; Phone Number: 861013911365592; Email: duanlian307@sina.com
• Study Contact Backup: Name: Han Cong, MD MS; Phone Number: 861013466346163; Email: hc82225@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High Altitude RIC group; 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; 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.
SHAM_COMPARATOR: High Altitude Sham group; 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; 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.
EXPERIMENTAL: Low Altitude RIC group; 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; 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.
SHAM_COMPARATOR: Low Altitude Sham group; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Affiliated Hospital to Academy of Military Medical Sciences
• Collaborators: Xuanwu Hospital, Beijing
• Investigators: Study Chair: Lian Duan, MD PHD, The 307th Hospital of Military Chinese People's Liberation Army

Publications and helpful links

General Publications

• Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.
• Meng R, Ding Y, Asmaro K, Brogan D, Meng L, Sui M, Shi J, Duan Y, Sun Z, Yu Y, Jia J, Ji X. Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment. Neurotherapeutics. 2015 Jul;12(3):667-77. doi: 10.1007/s13311-015-0358-6.
• Wilson MH, Newman S, Imray CH. The cerebral effects of ascent to high altitudes. Lancet Neurol. 2009 Feb;8(2):175-91. doi: 10.1016/S1474-4422(09)70014-6.
• Fan J, McCandliss BD, Sommer T, Raz A, Posner MI. Testing the efficiency and independence of attentional networks. J Cogn Neurosci. 2002 Apr 1;14(3):340-7. doi: 10.1162/089892902317361886.
• Posner MI, Petersen SE. The attention system of the human brain. Annu Rev Neurosci. 1990;13:25-42. doi: 10.1146/annurev.ne.13.030190.000325. No abstract available.
• Godfrey E, Chalder T, Ridsdale L, Seed P, Ogden J. Investigating the active ingredients of cognitive behaviour therapy and counselling for patients with chronic fatigue in primary care: developing a new process measure to assess treatment fidelity and predict outcome. Br J Clin Psychol. 2007 Sep;46(Pt 3):253-72. doi: 10.1348/014466506X147420.
• Wang Y, Meng R, Song H, Liu G, Hua Y, Cui D, Zheng L, Feng W, Liebeskind DS, Fisher M, Ji X. Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease. Stroke. 2017 Nov;48(11):3064-3072. doi: 10.1161/STROKEAHA.117.017691. Epub 2017 Oct 17.
• Twomey R, Wrightson J, Fletcher H, Avraam S, Ross E, Dekerle J. Exercise-induced Fatigue in Severe Hypoxia after an Intermittent Hypoxic Protocol. Med Sci Sports Exerc. 2017 Dec;49(12):2422-2432. doi: 10.1249/MSS.0000000000001371.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2018
• Primary Completion (ANTICIPATED): November 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (ACTUAL): November 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2018
• Last Update Submitted That Met QC Criteria: November 5, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: adult; cognitive function; remote ischemic conditioning; high altitude condition; blood oxygen levels
• Other Study ID Numbers: ERIC-HA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No