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

NCT04266639 | Completed

• 1 other identifier: ENOS
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

Remote Ischemic Conditioning; Neuroprotection

Outcome Measures

Primary Outcomes (2)

• RBC deformability will serve as a biomarker of the conditioning response and predictor of the clinical outcome in stroke patients.

  RBC deformability is measured as Deformability or Elongation Index (DI or EI, Rheoscan AnD-300, RheoMeditech, South Chorea). A higher EI at the optimum viscosity (300 Osmolality) indicates highly deformable RBCs indicative of better microcirculation, while a lower EI indicates rigid RBC's. Briefly, 6 µL of heparinized or EDTA treated fresh blood is mixed with 600-µL of polyvinylpyrrolidone (PVP) solution (300 Osm) and transferred to a disposable kit. The kit is placed inside the laser-assisted ectacytometer for automated read out, data and image collection as per the vendor's instructions.

  1 week

• RBC deformability will serve as a biomarker of the conditioning response and predictor of the clinical outcome in stroke patients

  For measurement of shear stress, 0,5 mL of heparinized or EDTA treated fresh blood is mixed with 600-µL of polyvinylpyrrolidone (PVP) solution (300 Osm) and transferred to a disposable kit. The kit is placed inside the laser-assisted ectacytometer for automated read out, data and image collection as per the vendor's instructions.

  1 week

Secondary Outcomes (14)

• Nitric oxide quantification using DAF-FM-Diacetate flowcytometry as a biomarker of the conditioning response

  1 week

• Nitric oxide quantification using DAF-FM-Diacetate flowcytometry as a predictor of the short term clinical outcome in stroke patients

  1 week

• RBC deformability presentation across stroke subtypes

  1 week

• RBC deformability in relation to infarct size/stroke severity

  1 week

• RBC erythrocrine dysfunction (NOS3) presentation across stroke subtypes

  9 months

Study Arms (3)

Remote Ischemic Conditioning

ACTIVE COMPARATOR

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

Device: Remote Ischemic Conditioning

Sham - Remote Ischemic Conditioning

SHAM COMPARATOR

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.

Device: Sham Remote Ischemic Conditioning

Controls

NO INTERVENTION

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

Interventions

Remote Ischemic Conditioning 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

Remote Ischemic Conditioning

Sham Remote Ischemic Conditioning DEVICE

Sham Comparator (Sham-RIC)

Sham - Remote Ischemic Conditioning

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Prior stroke, dementia or other known neurological condition Pregnancy
• Contraindications to MRI
• Investigators discretion
• Known upper extremity peripheral arterial stenosis Diabetes
• CONTROLS
• Independent in daily living (mRS 0-2) Ambulatory
• Legal competent
• Non vascular diagnosis (e.g. epilepsy, migraine etc.)
• Prior stroke, dementia or other known neurological condition
• Pregnancy
• Contraindications to MRI
• Investigators discretion
• Known upper extremity peripheral arterial stenosis Diabetes

Sponsors & Collaborators

• Grethe Andersen: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Brain Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Grethe Andersen, MD, DMSc

  Aarhus University Hospital, Department of Neurology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSc, Senior Consultant, MD

Model Details: Pilot, Single-center, Randomized, Patient-assessor blinded, Sham-controlled Trial

Study Record Dates

• First Submitted: February 3, 2020
• First Posted: February 12, 2020
• Study Start: July 29, 2020
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2021
• Last Updated: February 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)