Vascular DementiaPhase 2TRIC-VCINCT04109963
Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
A Phase 2 study testing Remote ischemic conditioning in people with Vascular Dementia and Cerebral Small Vessel Diseases, run by University of Calgary at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Vascular Dementia, Cerebral Small Vessel Diseases, Cerebral Small Vessel Ischaemic Disease
- What is being tested?
- Remote ischemic conditioning
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- 26 Sep 2019to 1 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
Karyn Fischer, MD, 403-210-7611, karyn.fischer@albertahealthservices.ca
Eric E Smith, RN, 403-944-1594, eesmith@ucalgary.ca
About this study
Official title: Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment
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.
Read the 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.
- Conditions
- Vascular Dementia, Cerebral Small Vessel Diseases, Cerebral Small Vessel Ischaemic Disease, Vascular Cognitive Impairment
- Being tested
- Remote ischemic conditioning
- Keywords
- vascular cognitive impairment, cerebral small vessel diseases, remote ischemic conditioning
- Medical subject headings
- Dementia, Vascular, Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic conditioningDevice
Remote ischemic conditioning therapy to the upper arm will be delivered by an automated device (RIC VCI) manufactured by Seagull Aps (Denmark).
| Study group | Role | What they receive |
|---|---|---|
| RIC once per day | Active comparator | 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. Receives: Device: Remote ischemic conditioning |
| RIC twice per day | Active comparator | 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. Receives: Device: Remote ischemic conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adherence
Proportion completing 80% or more sessions.
Measured: 30 days
Secondary outcomes (11)
Discontinuation
Cessation of device use
Measured: 30 days
Randomization
Proportion completing the run-in period and proceeding to randomization
Measured: 14 days
Physical examination
Proportion with signs of arm soft tissue or neurovascular injury
Measured: 30 days
Arm deep venous thrombosis
Arm deep venous thrombosis
Measured: 30 days
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]).
Measured: 30 days
MRI cerebral blood flow
Change in cerebral blood flow measured by arterial spin label MRI
Measured: 30 days and 90 days
MRI white matter hyperintensity volume
Change in white matter hyperintensity volume on FLAIR
Measured: 30 days and 90 days
MRI diffusion tensor imaging
Change in MRI peak skeletonized mean diffusivity
Measured: 30 days and 90 days
Global cognition
Change in Montreal Cognitive Assessment
Measured: 30 days and 90 days
Neuropsychological tests
Change in Trail-Making A and B
Measured: 30 days and 90 days
Neuropsychiatric symptoms
Change in Mild Behavioural Impairment Checklist
Measured: 30 days and 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2019
- Study start26 Sep 2019
- Primary completion31 Dec 2022 (estimated)
- Study completion1 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Vascular DementiaStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized, parallel arm, open-label, blinded end-point (PROBE) design.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canadian Consortium on Neurodegeneration in Aging
- Responsible party
- Sponsor
- Investigators
- Eric Smith, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04109963
- Sponsor's protocol ID
- REB19-0861
- Acronym
- TRIC-VCI
- Status last verified
- Aug 2021
- First submitted
- 27 Sep 2019
- Last updated
- 9 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Ganesh A, Camara-Lemarroy C, McCreary CR, Khnaijer B, Beaudin AE, Fischer K, Nukala N, Giuliani F, Barber PA, Black SE, Corbett D, Field TS, Frayne R, Hachinski VC, Ismail Z, Joundi RA, Mai LM, Sahlas DJ, Sharma M, Swartz RH, Smith EE. A Phase 2a randomized trial of once- versus twice-daily remote ischemic conditioning in vascular cognitive impairment (TRIC-VCI). Alzheimers Dement (N Y). 2026 Oct 23;12(4):e70335. doi: 10.1002/trc2.70335. eCollection 2026 Oct-Dec.
PubMed 42921033Ganesh 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.
PubMed 33055122
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment
- ClinicalTrials.gov ID
- NCT04109963
- Acronym / sponsor ID
- TRIC-VCI / REB19-0861
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canadian Consortium on Neurodegeneration in Aging
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 1 Mar 2023 (estimated)
- First posted
- 1 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, randomized, parallel arm, open-label, blinded end-point (PROBE) design.
| Arm | Type | Receives |
|---|---|---|
| RIC once per day | Active comparator | Device: Remote ischemic conditioningRIC 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 twice per day | Active comparator | Device: Remote ischemic conditioningRIC 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. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote ischemic conditioningRemote ischemic conditioning therapy to the upper arm will be delivered by an automated device (RIC VCI) manufactured by Seagull Aps (Denmark). | Device | RIC once per day, RIC twice per day |
Primary outcome
Adherence
Time frame: 30 days
Proportion completing 80% or more sessions.
11 secondary outcomes
Discontinuation
Time frame: 30 days
Randomization
Time frame: 14 days
Physical examination
Time frame: 30 days
Arm deep venous thrombosis
Time frame: 30 days
Pain
Time frame: 30 days
MRI cerebral blood flow
Time frame: 30 days and 90 days
MRI white matter hyperintensity volume
Time frame: 30 days and 90 days
MRI diffusion tensor imaging
Time frame: 30 days and 90 days
Global cognition
Time frame: 30 days and 90 days
Neuropsychological tests
Time frame: 30 days and 90 days
Neuropsychiatric symptoms
Time frame: 30 days and 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2022.
- Derived from this study: PubMed 42921033Ganesh A, Camara-Lemarroy C, McCreary CR, Khnaijer B, Beaudin AE, Fischer K, Nukala N, Giuliani F, Barber PA, Black SE, Corbett D, Field TS, Frayne R, Hachinski VC, Ismail Z, Joundi RA, Mai LM, Sahlas DJ, Sharma M, Swartz RH, Smith EE. A Phase 2a randomized trial of once- versus twice-daily remote ischemic conditioning in vascular cognitive impairment (TRIC-VCI). Alzheimers Dement (N Y). 2026 Oct 23;12(4):e70335. doi: 10.1002/trc2.70335. eCollection 2026 Oct-Dec.
- Derived from this study: PubMed 33055122Ganesh 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Smith, MD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Remote ischemic conditioning in people with Vascular Dementia and Cerebral Small Vessel Diseases, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eric E Smith, MD (1-403-944-1594, eesmith@ucalgary.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adherence (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04109963, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2022.