Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment

NCT ID: NCT04109963

Last Updated: 2022-06-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-26
• Study Completion Date: 2023-03-01

Brief Summary

Cerebral small vessel disease is a common cause of cognitive impairment. Remote ischemic pre-conditioning (RIC) is a technique to induce brief periods of limb ischemia-reperfusion that is hypothesized to increase tolerance of the brain to hypoperfusion and increase cerebral blood flow. Patients with cognitive impairment, preserved basic activities of daily living, and brain computed tomography (CT) or magnetic resonance imaging (MRI) evidence of confluent white matter hyperintensities or multiple brain infarcts will be randomized to either RIC performed once a day on one arm, or twice per day on one arm, for 30 days, to test tolerability and effects on MRI markers of blood flow.

Detailed Description

Cerebral small vessel disease (cSVD) accounts for 20-25% of all strokes and is the most common cause of vascular cognitive impairment (VCI) as well as a major contributor to mixed dementia, potentially interacting with Alzheimer's disease. Remote ischemic pre-conditioning (RIC) is a technique to induce brief periods of limb ischemia-reperfusion that is hypothesized to increase tolerance of the brain to hypoperfusion. This is a prospective, open-label randomized controlled clinical trial with blinded endpoint assessment (PROBE). Participants that complete a 14-day run-in period will be randomized to 30 days of either: a) RIC performed once per day on one arm, or b) RIC performed twice per day on one arm. Each RIC session will consist of 4 cycles of unilateral upper arm ischemia for 5 minutes followed by reperfusion for another 5 minutes, administered by modified blood pressure monitor (under an Investigational Trail Authorization from Health Canada). The primary outcome is tolerability, defined as the proportion in each trial arm that complete 80% or more of the assigned RIC sessions. Secondary outcomes will include pain scores, cognition, and MRI markers of cerebral blood flow and white matter integrity.

Conditions

Vascular Dementia; Cerebral Small Vessel Diseases; Cerebral Small Vessel Ischaemic Disease; Vascular Cognitive Impairment

Study Design

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

Study Groups

RIC once per day

RIC performed once a day on one arm. Each RIC session will consist of 4 cycles of unilateral or simultaneous bilateral upper arm ischemia for 5 minutes followed by reperfusion for another 5 minutes. The procedure will be performed by using an electric auto-control device with cuffs that inflate to a pressure of 200 mmHg during the ischemic period.

Group Type: ACTIVE_COMPARATOR

Remote ischemic conditioning

Intervention Type: DEVICE

Remote ischemic conditioning therapy to the upper arm will be delivered by an automated device (RIC VCI) manufactured by Seagull Aps (Denmark).

RIC twice per day

RIC performed twice a day on one arm, approximately 12 hours apart. Each RIC session will consist of 4 cycles of unilateral or simultaneous bilateral upper arm ischemia for 5 minutes followed by reperfusion for another 5 minutes. The procedure will be performed by using an electric auto-control device with cuffs that inflate to a pressure of 200 mmHg during the ischemic period.

Group Type: ACTIVE_COMPARATOR

Remote ischemic conditioning

Intervention Type: DEVICE

Remote ischemic conditioning therapy to the upper arm will be delivered by an automated device (RIC VCI) manufactured by Seagull Aps (Denmark).

Interventions

Remote ischemic conditioning

Remote ischemic conditioning therapy to the upper arm will be delivered by an automated device (RIC VCI) manufactured by Seagull Aps (Denmark).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Evidence of cerebral small vessel disease on CT or MRI, defined as either beginning confluent white matter hypodensities/hyperintensities (ARWMC scale) or two or more supratentorial infarcts
• Montreal Cognitive Assessment <25
• Concern on the part of the patient, caregiver, or clinician that there has been a decline from previous level of cognitive functioning
• Independent with basic activities of daily living (response (a) to questions 2, 4, 5, 6, 7, 8, 9, and 14 on the Bristol Activities of Daily Living scale).

Exclusion Criteria

• Cortical infarcts larger than 10 mm axial diameter
• Neuroimaging evidence of mass lesion, intracerebral hemorrhage, vascular malformation, or evidence of non-vascular disease such as hydrocephalus.
• Residence in long-term care facility.
• Other significant neurological or psychiatric disease (e.g. multiple sclerosis).
• Does not have a study partner who can provide corroborative information.
• English or French is not sufficiently proficient for clinical assessment and neuropsychological testing
• Montreal Cognitive Assessment score <13
• Unable to undergo MRI due to medical contraindications or inability to tolerate the procedure.
• Co-morbid medical illness that in the judgment of the study investigator makes it unlikely that the participant will be able to complete three months of study follow-up.
• On therapeutic anticoagulation with doses used for treatment of deep venous thrombosis, pulmonary embolism, or for stroke prevention in atrial fibrillation.
• Significant bleeding diathesis.
• Any symptomatic or previously known arm soft-tissue disease, vascular injury, or peripheral vascular disease
• Hypertension with systolic blood pressure >=180 mmHg despite medical treatment at the time of enrolment.
• Planned revascularization (any angioplasty or vascular surgery) within the next 3 months.
• Planned surgical procedure within the next 3 months.
• Currently receiving an investigational drug or device by other studies
• Blood pressure cuff cannot be sized properly (arm circumference is <23 cm or >42 cm)

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Canadian Consortium on Neurodegeneration in Aging

OTHER

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Smith, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Foothills Medical Centre

Calgary, Alberta, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Eric E Smith, MD

Role: CONTACT

eesmith@ucalgary.ca

1-403-944-1594

Karyn Fischer, RN

Role: CONTACT

Karyn.Fischer@albertahealthservices.ca

1-403-210-7611

Facility Contacts

Karyn Fischer, MD

Role: primary

karyn.fischer@albertahealthservices.ca

403-210-7611

Eric E Smith, RN

Role: backup

eesmith@ucalgary.ca

403-944-1594

References

Ganesh A, Barber P, Black SE, Corbett D, Field TS, Frayne R, Hachinski V, Ismail Z, Mai LM, McCreary CR, Sahlas D, Sharma M, Swartz RH, Smith EE. Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol. BMJ Open. 2020 Oct 14;10(10):e040466. doi: 10.1136/bmjopen-2020-040466.

Reference Type: DERIVED

PMID: 33055122 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

The dataset with individual de-identified participant data will be hosted on the University of Calgary PRISM dataverse once the main results results are published. The identifier will be assigned when the dataset is uploaded.

View Document

Other Identifiers

REB19-0861

Identifier Type: -

Identifier Source: org_study_id