Remote Preconditioning Over Time To Empower Cerebral Tissue

In this study, the investigators will enroll 60 patients. All patients will receive best
standard medical therapy for 2 years. In addition, the investigators will randomly assign 40
patients to undergo daily active remote ischemic preconditioning for 1 year, and 20 patients
to 1 year of standard medical therapy followed by 1 year of daily active remote ischemic
preconditioning. Patient structured interviews will be performed to assess if the treatment
is well tolerated and easy for stroke patients to use. Magnetic resonance (MR) pictures of
the brain will be used to determine if the active treatment stops the progression of brain
injury. Cognitive tests and wireless sensor technology measures will used to learn what
happens to the patient's brain and body during the active treatment.

After a subject consents to participate in the study, he/she will first participate in a
study screening phase to ensure a basic level of tolerability of Remote Ischemic Conditioning
(autoRIC™) device. The subject will undergo one full cycle of treatment under observation of
the study team, including 4 cycles of alternating 5 minute inflation and 5 minute off periods

If the subject indicates willingness to continue receiving such treatment (screening
success), she/she will enter the randomized trial phase, and be randomly allocated to the
treatment or control group.

If subject indicates unwillingness to continue receiving such treatment (screening failure),
he/she will not advance to the randomized phase of the trial. Screen failure subjects will be
followed up with a 3-day post-device screening phone call to ensure safety and obtain
information regarding any adverse events.

Inclusion Criteria:

I. Clinical

1. Clinical lacunar stroke syndrome within the past 6 months

2. Absence of signs or symptoms of cortical dysfunction

3. No proximal large vessel atherosclerosis, intracranial atherosclerosis or cerebellar
stroke.

4. No major cardioembolic source requiring anticoagulation or other specific therapy

II. Imaging

1. Magnetic Resonance Imaging (MRI) presence of a small subcortical ischemic, any 1 or
more of:

1. Diffusion-weighted imaging (DWI) lesion < 2.0cm in size at largest dimension and
corresponding to the clinical syndrome.

2. Well delineated focal hyperintensity <2.0 cm in size at largest dimension
(including rostro-caudal extent) on FLAIR or T2 and clearly corresponding to the
clinical syndrome. If other focal hyperintensities are present, the case will be
discussed with the principal investigator prior to randomization

3. Multiple (at least 2) hypointense lesions of size 0.3-1.5 cm at largest dimension
(including rostro-caudal extent) only in the cerebral hemispheres on FLAIR or T1
in patients whose qualifying event is clinically hemispheric

4. Well delinated hypointense lesion <1.5 cm in size at the largest dimension
(including rostro-caudal extent) on FLAIR or T1 corresponding to the clinical
syndrome. MRI must be done at least 1 months after the qualifying stroke

2. Absence of cortical stroke and large (> 1.5cm) subcortical stroke, recent or remote

3. White matter hyperintensity score of 2 (moderate) or 3 (severe) on the European Scale
of Age-Related White Matter Change

4. Absence of cerebral amyloid antipathy (CAA) as per Boston Criteria.

Exclusion Criteria:

1. Disabling stroke (Rankin Scale ≥4)

2. Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke

3. Age under 40 years

4. High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease,
etc.)

5. Anticipated requirement for long term use of anticoagulants (e.g. recurrent deep
venous thrombosis (DVT)

6. Prior cortical or retinal stroke (diagnosed either clinically or by neuroimaging), or
other prior cortical or retinal transient ischemic attack (TIA)

7. Prior ipsilateral carotid endarterectomy

8. Impaired renal function: estimated GFR <40

9. Intolerance or contraindications to aspirin or clopidogrel (including
thrombocytopenia, prolonged INR)

10. Mini Mental Status Exam score < 24 (adjusted for age and education)

11. Medical contraindication to MRI

12. Pregnancy or women of child-bearing age who are not following an effective method of
contraception

13. Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound
the neurological or functional outcome evaluations

14. SBP <90 or > 200

15. Known history of limb vascular disease, limb vascular bypass surgery, or limb deep
venous thrombosis

16. Prisoners

17. Homeless individuals

18. Patient unable to give informed consent and no available legally authorized
representative to provide informed consent

19. Patient unlikely to be compliant with therapy/ unwilling to return for follow up
visits

20. Concurrent participation in another study with investigational drug or device
treatment

21. Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic
diathesis, drug abuse)