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

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ClinicalTrials.gov Identifier: NCT04109963
Recruitment Status : Recruiting
First Posted : October 1, 2019
Last Update Posted : October 2, 2019
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Canadian Consortium on Neurodegeneration in Aging
Information provided by (Responsible Party):
University of Calgary

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.

Condition or disease Intervention/treatment Phase
Vascular Dementia Cerebral Small Vessel Diseases Cerebral Small Vessel Ischaemic Disease Vascular Cognitive Impairment Device: Remote ischemic conditioning Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, randomized, parallel arm, open-label, blinded end-point (PROBE) design.
Masking: Single (Outcomes Assessor)
Masking Description: Outcomes will be assessed masked to treatment assignment. Participants will be aware of treatment assignment.
Primary Purpose: Treatment
Official Title: Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment
Actual Study Start Date : September 26, 2019
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : October 1, 2020

Arm Intervention/treatment
Active Comparator: 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.
Device: 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).

Active Comparator: 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.
Device: 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).




Primary Outcome Measures :
  1. Adherence [ Time Frame: 30 days ]
    Proportion completing 80% or more sessions.


Secondary Outcome Measures :
  1. Discontinuation [ Time Frame: 30 days ]
    Cessation of device use

  2. Randomization [ Time Frame: 14 days ]
    Proportion completing the run-in period and proceeding to randomization

  3. Physical examination [ Time Frame: 30 days ]
    Proportion with signs of arm soft tissue or neurovascular injury

  4. Arm deep venous thrombosis [ Time Frame: 30 days ]
    Arm deep venous thrombosis

  5. Pain [ Time Frame: 30 days ]
    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]).

  6. MRI cerebral blood flow [ Time Frame: 30 days and 90 days ]
    Change in cerebral blood flow measured by arterial spin label MRI

  7. MRI white matter hyperintensity volume [ Time Frame: 30 days and 90 days ]
    Change in white matter hyperintensity volume on FLAIR

  8. MRI diffusion tensor imaging [ Time Frame: 30 days and 90 days ]
    Change in MRI peak skeletonized mean diffusivity

  9. Global cognition [ Time Frame: 30 days and 90 days ]
    Change in Montreal Cognitive Assessment

  10. Neuropsychological tests [ Time Frame: 30 days and 90 days ]
    Change in Trail-Making A and B

  11. Neuropsychiatric symptoms [ Time Frame: 30 days and 90 days ]
    Change in Mild Behavioural Impairment Checklist



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04109963


Contacts
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Contact: Eric E Smith, MD 1-403-944-1594 eesmith@ucalgary.ca
Contact: Karyn Fischer, RN 1-403-210-7611 Karyn.Fischer@albertahealthservices.ca

Locations
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Canada, Alberta
Foothills Medical Centre Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Karyn Fischer, MD    403-210-7611    karyn.fischer@albertahealthservices.ca   
Contact: Eric E Smith, RN    403-944-1594    eesmith@ucalgary.ca   
Sponsors and Collaborators
University of Calgary
Canadian Institutes of Health Research (CIHR)
Canadian Consortium on Neurodegeneration in Aging
Investigators
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Principal Investigator: Eric Smith, MD University of Calgary
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: Not yet available
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Calgary
ClinicalTrials.gov Identifier: NCT04109963    
Other Study ID Numbers: REB19-0861
First Posted: October 1, 2019    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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.
Access Criteria: Open to the public.
URL: https://dataverse.scholarsportal.info/dataverse/calgary

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Calgary:
vascular cognitive impairment, cerebral small vessel diseases, remote ischemic conditioning
Additional relevant MeSH terms:
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Dementia, Vascular
Cerebral Small Vessel Diseases
Ischemia
Cognitive Dysfunction
Pathologic Processes
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases