Cerebral Small Vessel Disease, Cognitive Decline, Ischemic Stroke
Conditions
Keywords
ischemic preconditioning, remote ischemic preconditioning, ischemic stroke, white matter disease, cerebral small vessel disease, cognitive decline, leukoaraiosis, diffusion tensor imaging, white matter hyper intensity score, European scale of age-related white matter change
Brief summary
Previous studies in animals and humans has shown that brief periods of reduced blood flow to one organ or tissue in the body can help protect other tissues from subsequent injury caused by reduced blood flow such as a stroke. This phenomenon is known as remote ischemic preconditioning and may help protect brain cells after a stroke. The investigators are studying a specific stroke type called subcortical stroke that is very common and has a high rate of recurrent stroke and cognition problems despite intensive prevention measures.
Detailed description
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.
Interventions
DEVICEIschemic Preconditioning
Patients will undergo ischemic preconditioning once or twice daily for up to four 5-minutes cycles of bilateral upper extremity ischemia separated by 5-minute periods of reperfusion.
Sponsors
American Heart Association
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Duration of Adherence to Ischemic Preconditioning Procedure | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Limb Ischemia as Assessed by the Preconditioning Device | 12 months |
| Patient Self-reported Comfort-discomfort on a Scale of 1-5, With Lowest Score = Very Comfortable and 5 = Very Uncomfortable | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Medical Therapy Only Intensive standard medical secondary prevention stroke treatment as per the recommendations of the American Heart Association/American Stroke Association national guidelines. | 2 |
| Ischemic Preconditioning + Medical Patients will receive treatment with Cell Aegis remote ischemic preconditioning device once or twice daily for one year. The procedure will consist of up to four 5-minute cycles of bilateral upper extremity ischemia separated by five minutes of reperfusion. Patients will also receive intensive standard medical secondary prevention stroke treatment as per the American Heart Association/American Stroke Association national guidelines.
Ischemic Preconditioning: Patients will undergo ischemic preconditioning once or twice daily for up to four 5-minutes cycles of bilateral upper extremity ischemia separated by 5-minute periods of reperfusion. | 4 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 4 |
Baseline characteristics
| Characteristic | Ischemic Preconditioning + Medical | Total | Medical Therapy Only |
|---|---|---|---|
| Age, Continuous | 63.7 years | 67.1 years | 74 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 0 / 2 | 0 / 4 |
| serious Total, serious adverse events | 0 / 2 | 0 / 4 |
Outcome results
Primary
Duration of Adherence to Ischemic Preconditioning Procedure
Time frame: 12 months
Population: The medical intervention arm did not undergo ischemic preconditioning
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ischemic Preconditioning + Medical | Duration of Adherence to Ischemic Preconditioning Procedure | 3 Months |
Secondary
Limb Ischemia as Assessed by the Preconditioning Device
Time frame: 12 months
Population: Data were not collected since no participants reached the 12-month follow-up
Secondary
Patient Self-reported Comfort-discomfort on a Scale of 1-5, With Lowest Score = Very Comfortable and 5 = Very Uncomfortable
Time frame: 12 months
Population: Data were not collected since no participants reached the 12-month follow-up