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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

Tracking Information
First Submitted Date  ICMJE September 27, 2019
First Posted Date  ICMJE October 1, 2019
Last Update Posted Date October 2, 2019
Actual Study Start Date  ICMJE September 26, 2019
Estimated Primary Completion Date October 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2019)
Adherence [ Time Frame: 30 days ]
Proportion completing 80% or more sessions.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
  • Discontinuation [ Time Frame: 30 days ]
    Cessation of device use
  • Randomization [ Time Frame: 14 days ]
    Proportion completing the run-in period and proceeding to randomization
  • Physical examination [ Time Frame: 30 days ]
    Proportion with signs of arm soft tissue or neurovascular injury
  • Arm deep venous thrombosis [ Time Frame: 30 days ]
    Arm deep venous thrombosis
  • 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]).
  • MRI cerebral blood flow [ Time Frame: 30 days and 90 days ]
    Change in cerebral blood flow measured by arterial spin label MRI
  • MRI white matter hyperintensity volume [ Time Frame: 30 days and 90 days ]
    Change in white matter hyperintensity volume on FLAIR
  • MRI diffusion tensor imaging [ Time Frame: 30 days and 90 days ]
    Change in MRI peak skeletonized mean diffusivity
  • Global cognition [ Time Frame: 30 days and 90 days ]
    Change in Montreal Cognitive Assessment
  • Neuropsychological tests [ Time Frame: 30 days and 90 days ]
    Change in Trail-Making A and B
  • Neuropsychiatric symptoms [ Time Frame: 30 days and 90 days ]
    Change in Mild Behavioural Impairment Checklist
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2019)
  • Discontinuation [ Time Frame: 30 days ]
    Cessation of device use
  • Randomization [ Time Frame: 14 days ]
    Proportion completing the run-in period and proceeding to randomization
  • Physical examination [ Time Frame: 30 days ]
    Proportion with signs of arm soft tissue or neurovascular injury
  • Arm deep venous thrombosis [ Time Frame: 30 days ]
    Arm deep venous thrombosis
  • Pain [ Time Frame: 30 days ]
    Mean peak and end-cycle pain levels reported using the Visual Analog Scale
  • MRI cerebral blood flow [ Time Frame: 30 days and 90 days ]
    Change in cerebral blood flow measured by arterial spin label MRI
  • MRI white matter hyperintensity volume [ Time Frame: 30 days and 90 days ]
    Change in white matter hyperintensity volume on FLAIR
  • MRI diffusion tensor imaging [ Time Frame: 30 days and 90 days ]
    Change in MRI peak skeletonized mean diffusivity
  • Global cognition [ Time Frame: 30 days and 90 days ]
    Change in Montreal Cognitive Assessment
  • Neuropsychological tests [ Time Frame: 30 days and 90 days ]
    Change in Trail-Making A and B
  • Neuropsychiatric symptoms [ Time Frame: 30 days and 90 days ]
    Change in Mild Behavioural Impairment Checklist
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
Official Title  ICMJE Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Vascular Dementia
  • Cerebral Small Vessel Diseases
  • Cerebral Small Vessel Ischaemic Disease
  • Vascular Cognitive Impairment
Intervention  ICMJE 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).
Study Arms  ICMJE
  • 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.
    Intervention: Device: Remote ischemic conditioning
  • 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.
    Intervention: Device: Remote ischemic conditioning
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 27, 2019)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2020
Estimated Primary Completion Date October 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eric E Smith, MD 1-403-944-1594 eesmith@ucalgary.ca
Contact: Karyn Fischer, RN 1-403-210-7611 Karyn.Fischer@albertahealthservices.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04109963
Other Study ID Numbers  ICMJE REB19-0861
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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
Responsible Party University of Calgary
Study Sponsor  ICMJE University of Calgary
Collaborators  ICMJE
  • Canadian Institutes of Health Research (CIHR)
  • Canadian Consortium on Neurodegeneration in Aging
Investigators  ICMJE
Principal Investigator: Eric Smith, MD University of Calgary
PRS Account University of Calgary
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP