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Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment (TRIC-VCI)

Primary Purpose

Vascular Dementia, Cerebral Small Vessel Diseases, Cerebral Small Vessel Ischaemic Disease

Status

Unknown status

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Remote ischemic conditioning

About this trial

This is an interventional treatment trial for Vascular Dementia focused on measuring vascular cognitive impairment, cerebral small vessel diseases, remote ischemic conditioning

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Foothills Medical CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

RIC once per day

RIC twice per day

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Adherence

Proportion completing 80% or more sessions.

Secondary Outcome Measures

Discontinuation

Cessation of device use

Randomization

Proportion completing the run-in period and proceeding to randomization

Physical examination

Proportion with signs of arm soft tissue or neurovascular injury

Arm deep venous thrombosis

Pain

Mean peak and end-cycle pain levels reported using the Numeric Rating Scale for pain (based on subjective report, ranging from 0 [no pain] to 10 [worst possible pain]).

MRI cerebral blood flow

Change in cerebral blood flow measured by arterial spin label MRI

MRI white matter hyperintensity volume

Change in white matter hyperintensity volume on FLAIR

MRI diffusion tensor imaging

Change in MRI peak skeletonized mean diffusivity

Global cognition

Change in Montreal Cognitive Assessment

Neuropsychological tests

Change in Trail-Making A and B

Neuropsychiatric symptoms

Change in Mild Behavioural Impairment Checklist

Full Information

NCT ID

NCT04109963

First Posted

September 27, 2019

Last Updated

June 7, 2022

Sponsor

University of Calgary

Collaborators

Canadian Institutes of Health Research (CIHR), Canadian Consortium on Neurodegeneration in Aging

1. Study Identification

Unique Protocol Identification Number

NCT04109963

Brief Title

Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment

Acronym

TRIC-VCI

Official Title

Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Unknown status

Study Start Date

September 26, 2019 (Actual)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

March 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Calgary

Collaborators

Canadian Institutes of Health Research (CIHR), Canadian Consortium on Neurodegeneration in Aging

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

vascular cognitive impairment, cerebral small vessel diseases, remote ischemic conditioning

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Prospective, randomized, parallel arm, open-label, blinded end-point (PROBE) design.

Masking

Outcomes Assessor

Masking Description

Outcomes will be assessed masked to treatment assignment. Participants will be aware of treatment assignment.

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

RIC once per day

Arm Type

Active Comparator

Arm Description

Arm Title

RIC twice per day

Arm Type

Active Comparator

Arm Description

Intervention Type

Device

Intervention Name(s)

Remote ischemic conditioning

Intervention Description

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

Primary Outcome Measure Information:

Title

Adherence

Description

Proportion completing 80% or more sessions.

Time Frame

30 days

Secondary Outcome Measure Information:

Title

Discontinuation

Description

Cessation of device use

Time Frame

30 days

Title

Randomization

Description

Proportion completing the run-in period and proceeding to randomization

Time Frame

14 days

Title

Physical examination

Description

Proportion with signs of arm soft tissue or neurovascular injury

Time Frame

30 days

Title

Arm deep venous thrombosis

Description

Arm deep venous thrombosis

Time Frame

30 days

Title

Pain

Description

Mean peak and end-cycle pain levels reported using the Numeric Rating Scale for pain (based on subjective report, ranging from 0 [no pain] to 10 [worst possible pain]).

Time Frame

30 days

Title

MRI cerebral blood flow

Description

Change in cerebral blood flow measured by arterial spin label MRI

Time Frame

30 days and 90 days

Title

MRI white matter hyperintensity volume

Description

Change in white matter hyperintensity volume on FLAIR

Time Frame

30 days and 90 days

Title

MRI diffusion tensor imaging

Description

Change in MRI peak skeletonized mean diffusivity

Time Frame

30 days and 90 days

Title

Global cognition

Description

Change in Montreal Cognitive Assessment

Time Frame

30 days and 90 days

Title

Neuropsychological tests

Description

Change in Trail-Making A and B

Time Frame

30 days and 90 days

Title

Neuropsychiatric symptoms

Description

Change in Mild Behavioural Impairment Checklist

Time Frame

30 days and 90 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Eric E Smith, MD

Phone

1-403-944-1594

eesmith@ucalgary.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Karyn Fischer, RN

Phone

1-403-210-7611

Karyn.Fischer@albertahealthservices.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eric Smith, MD

Organizational Affiliation

University of Calgary

Official's Role

Principal Investigator

Facility Information:

Facility Name

Foothills Medical Centre

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 2T9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Karyn Fischer, MD

Phone

403-210-7611

karyn.fischer@albertahealthservices.ca

First Name & Middle Initial & Last Name & Degree

Eric E Smith, RN

Phone

403-944-1594

eesmith@ucalgary.ca

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The completely de-identified study dataset will be posted to the University of Calgary section of the PRISM dataverse at the time of publication of the main study results in a peer-reviewed journal.

IPD Sharing Time Frame

The study dataset will be made publicly available at the time of publication of the main study results in a peer-reviewed journal.

IPD Sharing Access Criteria

Open to the public.

IPD Sharing URL

https://dataverse.scholarsportal.info/dataverse/calgary

Citations:

PubMed Identifier

33055122

Citation

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.

Results Reference

derived

Available IPD and Supporting Information:

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://dataverse.scholarsportal.info/dataverse/calgary

Available IPD/Information Identifier

Not yet available

Available IPD/Information Comments

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.

Learn more about this trial

Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment

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