Assessment of remote ischemic conditioning delivery with optical sensor in acute ischemic stroke: Randomised clinical trial protocol

Abstract

Background: Remote ischemic conditioning (RIC) is delivered by a blood pressure cuff over the limb, raising pressure 50 mmHg above the systolic blood pressure, to a maximum of 200 mmHg. The cuff is inflated for five minutes and then deflated for five minutes in a sequential ischemia-reperfusion cycle 4-5 times per session. Elevated pressure in the limb may be associated with discomfort and consequently reduced compliance. Continuous assessment of relative blood concentration and oxygenation with a tissue reflectance spectroscopy (a type of optical sensor device) placed over the forearm during the RIC sessions of the arm will allow us to observe the effect of inflation and deflation of the pressure cuff. We hypothesize, in patients with acute ischemic stroke (AIS) and small vessel disease, RIC delivered together with a tissue reflectance sensor will be feasible.

Methods: The study is a prospective, single-center, randomized control trial testing the feasibility of the device. Patients with AIS within 7 days from symptoms onset; who also have small vessel disease will be randomized 2:1 to intervention or sham control arms. All patients randomized to the intervention arm will receive 5 cycles of ischemia/reperfusion in the non-paralyzed upper limb with a tissue reflectance sensor and patients in the sham control arm will receive pressure by keeping the cuff pressure at 30 mmHg for 5 minutes. A total of 51 patients will be randomized, 17 in the sham control arm and 34 in the intervention arm. The primary outcome measure will be the feasibility of RIC delivered for 7 days or at the time of discharge. The secondary device-related outcome measures are fidelity of RIC delivery and the completion rate of intervention. The secondary clinical outcome includes a modified Rankin scale, recurrent stroke and cognitive assessment at 90 days.

Discussion: RIC delivery together with a tissue reflectance sensor will allow insight into the blood concentration and blood oxygenation changes in the skin. This will allow individualized delivery of the RIC and improve compliance.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT05408130, June 7, 2022.

Conflict of interest statement

No authors have competing interests.

Copyright: © 2023 Nair et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Figures

Fig 1. Study schedule.

Fig 2. The setup for the remote ischemic conditioning delivery in the arm muscles.

The tissue reflectance sensor is placed over the forearm and covered with an opaque cloth band for better-quality data acquisition and holding the sensor in place. The processor transmits the data in real time with a ZigBee protocol, with a mini-tower connected to the laptop for power. The dashboard synchronizes the data from the BP device and tissue reflectance sensor to display in real time.

Fig 3. Systolic blood pressure (SBP), blood concentration (BloodConc), and blood oxygenation changes (Ox1 and Ox 2) during a remote ischemic conditioning therapy session with 5 cycles in the intervention arm and sham arm.

Intervention Arm: The SBP (blue) was maintained at 180 mmHg for the initial two cycles and 150 mmHg for the remaining three cycles. The BloodConc (orange) increases with inflation and decreases with deflation. Ox1 and Ox2 (gray and yellow) decrease with inflation and bounces back with deflation. There is transient reactive hyperemia (increase in Ox1 and Ox2) corresponding to the early phase of deflation. There was no apparent change noted in the BloodConc, Ox1 and Ox2 after the change in the blood pressure from 180 mmHg to 150 mmHg. Sham Arm: the SBP was maintained at 30 mmHg for the five cycles. The BloodConc, Ox1 and Ox2 change inconsistently.