Chronic Remote Ischemic Conditioning in Vascular Cognitive Impairment: A Dose Escalation Study

Study Overview
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Brief Summary
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To evaluate the dose-response of relevant blood biomarkers to remote ischemic conditioning in patients with age-related cerebral white matter hyperintensities on MRI, in preparation for a subsequent larger efficacy trial.

Detailed Description
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Objective: The objective of this early phase study is to evaluate the dose-response of relevant blood biomarkers to remote ischemic conditioning in preparation for a subsequent larger efficacy trial. In addition, we will evaluate the tolerability and adherence to the treatment protocol. Aim: We aim to measure blood biomarkers in response to daily remote ischemic conditioning (RIC) using a dose escalation study design in 40 patients with age-related cerebral white matter hyperintensities on MRI. Hypothesis: We hypothesize that there will be a significant change in the biomarker levels in a dose dependent fashion.

Official Title
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Chronic Remote Ischemic Conditioning in Vascular Cognitive Impairment: A Dose Escalation Study

Conditions
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Age-related Cerebral White Matter Changes, Cognition Disorder

Intervention / Treatment
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* Device: remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥55 years Head MRI in the past 6 months showing no more than moderate age related cerebral white matter changes (Fazekas score 0-2). Able to walk without assistance & independently perform basic activities of daily living. Able to understand this study and agree for a valid consent. Exclusion Criteria: Prior non-lacunar (cortical) stroke. 2. Unable to cooperate with the use of the conditioning device. 3. Confounding illness that might interfere with the interpretation of results (such as active malignancy or multiple sclerosis). 4. Contraindication to transient arm ischemia in either arm (such as symptomatic peripheral artery disease).

Ages Eligible for Study
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Minimum Age: 56 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: sham<br>BP cuff bilateral arm compression to 50 mmHg. | Device: remote ischemic conditioning<br>* suprasystolic BP sequential compression of both arms with blood pressure cuffs for 5 min on/off for 4 cycles.<br>* Other names: RIC;|
| Active Comparator: dose 1<br>BP cuff bilateral arm compression to 50 mmHg above systolic BP for 2.5 minutes on/off for 4 cycles every other day. | Device: remote ischemic conditioning<br>* suprasystolic BP sequential compression of both arms with blood pressure cuffs for 5 min on/off for 4 cycles.<br>* Other names: RIC;|
| Active Comparator: dose 2<br>BP cuff bilateral arm compression to 50 mmHg above systolic BP for 5 minutes on/off for 4 cycles every other day. | Device: remote ischemic conditioning<br>* suprasystolic BP sequential compression of both arms with blood pressure cuffs for 5 min on/off for 4 cycles.<br>* Other names: RIC;|
| Active Comparator: dose 3<br>BP cuff bilateral arm compression to 50 mmHg above systolic BP for 5 minutes on/off once daily. | Device: remote ischemic conditioning<br>* suprasystolic BP sequential compression of both arms with blood pressure cuffs for 5 min on/off for 4 cycles.<br>* Other names: RIC;|
| Active Comparator: dose 4<br>BP cuff bilateral arm compression to 50 mmHg above systolic BP for 5 minutes on/off twice daily. | Device: remote ischemic conditioning<br>* suprasystolic BP sequential compression of both arms with blood pressure cuffs for 5 min on/off for 4 cycles.<br>* Other names: RIC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC deformability index | from baseline to 4 weeks of treatment and one week off treatment | 5 weeks total study duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inflammatory and anti-inflammatory Interleukins | ability to tolerate and adhere to protocol treatments. | 5 weeks | 
| tolerability | any discontinuation and adverse events during treatment. | 4 weeks |