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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
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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
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

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
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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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

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
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.
Arm Title
RIC twice per day
Arm Type
Active Comparator
Arm Description
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.
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
No
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
Email
eesmith@ucalgary.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Karyn Fischer, RN
Phone
1-403-210-7611
Email
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
Email
karyn.fischer@albertahealthservices.ca
First Name & Middle Initial & Last Name & Degree
Eric E Smith, RN
Phone
403-944-1594
Email
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.

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Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment

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