Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment

Vascular Dementia Clinical Trial

— TRIC-VCI  

Official title:

Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04109963
• Other study ID #: REB19-0861
• Status: Recruiting
• Phase: Phase 2
• Start date: September 26, 2019
• Est. completion date: March 1, 2023

Study information

• Verified date: August 2021
• Source: University of Calgary
• Contact: Eric E Smith, MD
• Phone: 1-403-944-1594
• Email: eesmith[@]ucalgary.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: March 1, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cerebral Small Vessel Diseases
• Cerebral Small Vessel Ischaemic Disease
• Cognitive Dysfunction
• Dementia, Vascular
• Ischemia
• Vascular Cognitive Impairment
• Vascular Dementia

Intervention

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).

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta

Sponsors (3)

Lead Sponsor	Collaborator
University of Calgary	Canadian Consortium on Neurodegeneration in Aging, Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adherence	Proportion completing 80% or more sessions.	30 days
Secondary	Discontinuation	Cessation of device use	30 days
Secondary	Randomization	Proportion completing the run-in period and proceeding to randomization	14 days
Secondary	Physical examination	Proportion with signs of arm soft tissue or neurovascular injury	30 days
Secondary	Arm deep venous thrombosis	Arm deep venous thrombosis	30 days
Secondary	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]).	30 days
Secondary	MRI cerebral blood flow	Change in cerebral blood flow measured by arterial spin label MRI	30 days and 90 days
Secondary	MRI white matter hyperintensity volume	Change in white matter hyperintensity volume on FLAIR	30 days and 90 days
Secondary	MRI diffusion tensor imaging	Change in MRI peak skeletonized mean diffusivity	30 days and 90 days
Secondary	Global cognition	Change in Montreal Cognitive Assessment	30 days and 90 days
Secondary	Neuropsychological tests	Change in Trail-Making A and B	30 days and 90 days
Secondary	Neuropsychiatric symptoms	Change in Mild Behavioural Impairment Checklist	30 days and 90 days