Rheo-Erythrocrine Dysfunction as a Biomarker for RIC Treatment in Acute Ischemic Stroke

NCT ID: NCT04266639

Last Updated: 2022-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-29
• Study Completion Date: 2021-07-31

Brief Summary

This study aims to investigate whether Remote Ischemic Conditioning (RIC) improves rheo-erythrocrine dysfunction in acute ischemic stroke

Detailed Description

Stroke is a leading cause of death and disability worldwide. Of all strokes, 85% are ischemic strokes caused by a thrombus or an embolus. The additional 15% are caused by hemorrhage. Currently the only approved treatments for ischemic strokes are thrombolysis given within 4.5 hours and thrombectomy performed within 6 hours of symptom onset - in some cases up to 24 hours. The majority of stroke patients are not however eligible for acute reperfusion therapy, mainly due to time constrains and late presentation. Novel neuroprotective strategies available for all stroke patients are thus urgently needed.

Remote Ischemic Conditioning (RIC) is a simple intervention in which transient ischemia is induced in an extremity by repetitive inflation-deflation of a blood pressure cuff. It remains uncertain exactly how the protective effect of RIC is transmitted and communicated between the extremity and the brain. Both humoral, immunological and neuronal pathways seem to be involved. Treatment with RIC and has proven to be a safe, feasible and low-cost treatment in clinical settings.

Biomarkers of the RIC treatment is a new area of stroke research and are important to establish in order to assess and predict responders of the conditioning treatment. Rheo-erythrocrine dysfunction of the Red Blood Cell (RBC) is a novel biomarker in both ischemic strokes in general and on the effect of RIC. Red Blood Cells with a diameter of 6-8 μm must be highly deformable in order to deliver oxygen to brain tissue by travelling through micro vessels with a diameter of just 2-3 μm. RBC's can carry nitric oxide as NO2-/s-nitrosylated proteins. These proteins improve RBC deformability and induce hypoxic vasodilation thereby improving passage through the microvasculature. RBC's also express Erythrocyte Nitric Oxide Synthase 3, which regulate the rheo-erythrocrine function. Erythrocyte Nitric Oxide Synthase 3 is activated by shear stress and provide an extra source of NO for hypoxic vasodilation. Preliminary data have shown that experimental stroke on mice seems to cause a rheo-erythrocrine dysfunction of the RBC's leading to a loss of deformability. The RBC's become rigid, which can lead to occlusion of micro vessels in the brain and further ischemic damage. Loss of deformability can be measured as a reduced Elongation Index (EI) by ektacytometry and may be attenuated by RIC.

Conditions

Stroke, Acute; Ischemic Stroke; Cerebrovascular Disorders; Central Nervous System Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Remote Ischemic Conditioning

Remote Ischemic Conditioning (RIC) is applied during the in-hospital phase using an automated RIC device.

Treatment characteristics: Five cycles (50 minutes), each consisting of five minutes of cuff inflation followed by five minutes of cuff deflation. The cuff pressure will be 200 mmHg; if initial systolic blood pressure is above 175 mmHg, the cuff is automatically inflated to 35 mmHg above the systolic blood pressure.

• Initial Remote Ischemic Conditioning: < 2 hours from inclusion
• Remote Ischemic Postconditioning: twice daily for 7 days

Usual care with or without acute reperfusion therapy

Group Type: ACTIVE_COMPARATOR

Remote Ischemic Conditioning

Intervention Type: DEVICE

RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion

Sham - Remote Ischemic Conditioning

Sham Remote Ischemic Conditioning (Sham-RIC) is applied during the in-hospital phase using an automated Sham-RIC device.

Treatment characteristics: Five cycles (50 minutes), each consisting of five minutes of cuff inflation followed by five minutes of cuff deflation. The cuff pressure will be always be 20 mmHg.

• Initial Sham Remote Ischemic Conditioning: < 2 hours from inclusion
• Sham Remote ischemic Postconditioning: twice daily for 7 days

Usual care with or without acute reperfusion therapy.

Group Type: SHAM_COMPARATOR

Sham Remote Ischemic Conditioning

Intervention Type: DEVICE

Sham Comparator (Sham-RIC)

Controls

The control group will not receive treatment with Remote Ischemic Conditioning.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Remote Ischemic Conditioning

RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion

Intervention Type: DEVICE

Sham Remote Ischemic Conditioning

Sham Comparator (Sham-RIC)

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Onset to randomization < 48 hours
• Independent in daily living (mRS 0-2)
• Legal competent
• Ambulatory
• Documented ischemic stroke on baseline MRI

• Independent in daily living (mRS 0-2) Ambulatory
• Legal competent
• Non vascular diagnosis (e.g. epilepsy, migraine etc.)

Exclusion Criteria

• Prior stroke, dementia or other known neurological condition Pregnancy
• Contraindications to MRI
• Investigators discretion
• Known upper extremity peripheral arterial stenosis Diabetes

CONTROLS

• Prior stroke, dementia or other known neurological condition
• Pregnancy
• Contraindications to MRI
• Investigators discretion
• Known upper extremity peripheral arterial stenosis Diabetes

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grethe Andersen

OTHER

Sponsor Role: lead

Responsible Party

Grethe Andersen

Professor, DMSc, Senior Consultant, MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Grethe Andersen, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital, Department of Neurology

Locations

Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

ENOS

Identifier Type: -

Identifier Source: org_study_id