Clinical trial NCT04109963: Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
Official title: Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: 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
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Canadian Consortium on Neurodegeneration in Aging
First posted: 2019-10-01
Enrollment: 24
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, parallel arm, open-label, blinded end-point (PROBE) design.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Adherence
timeFrame: 30 days
Secondary outcomes:
measure: Discontinuation
timeFrame: 30 days
measure: Randomization
timeFrame: 14 days
measure: Physical examination
timeFrame: 30 days
measure: Arm deep venous thrombosis
timeFrame: 30 days
measure: Pain
timeFrame: 30 days
measure: MRI cerebral blood flow
timeFrame: 30 days and 90 days
measure: MRI white matter hyperintensity volume
timeFrame: 30 days and 90 days
measure: MRI diffusion tensor imaging
timeFrame: 30 days and 90 days
measure: Global cognition
timeFrame: 30 days and 90 days
measure: Neuropsychological tests
timeFrame: 30 days and 90 days
measure: Neuropsychiatric symptoms
timeFrame: 30 days and 90 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
Study officials:
affiliation: University of Calgary
name: Eric Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.