Remote Preconditioning Over Time To Empower Cerebral Tissue

NCT02169739 | Terminated Results DMC

• 1 other identifier: AHA-000-376
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke; Cerebral Small Vessel Disease; Cognitive Decline

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

Outcome Measures

Primary Outcomes (1)

• Duration of Adherence to Ischemic Preconditioning Procedure

  12 months

Secondary Outcomes (2)

• 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

Study Arms (2)

Medical therapy only

NO INTERVENTION

Intensive standard medical secondary prevention stroke treatment as per the recommendations of the American Heart Association/American Stroke Association national guidelines.

Ischemic Preconditioning + Medical

ACTIVE COMPARATOR

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.

Device: Ischemic Preconditioning

Interventions

Ischemic Preconditioning DEVICE

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.

Ischemic Preconditioning + Medical

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I. Clinical
• Clinical lacunar stroke syndrome within the past 6 months
• Absence of signs or symptoms of cortical dysfunction
• No proximal large vessel atherosclerosis, intracranial atherosclerosis or cerebellar stroke.
• No major cardioembolic source requiring anticoagulation or other specific therapy
• II. Imaging
• Magnetic Resonance Imaging (MRI) presence of a small subcortical ischemic, any 1 or more of:
• Diffusion-weighted imaging (DWI) lesion \< 2.0cm in size at largest dimension and corresponding to the clinical syndrome.
• 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
• 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
• 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
• Absence of cortical stroke and large (\> 1.5cm) subcortical stroke, recent or remote
• White matter hyperintensity score of 2 (moderate) or 3 (severe) on the European Scale of Age-Related White Matter Change
• Absence of cerebral amyloid antipathy (CAA) as per Boston Criteria.

You may not qualify if:

• Disabling stroke (Rankin Scale ≥4)
• Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke
• Age under 40 years
• High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc.)
• Anticipated requirement for long term use of anticoagulants (e.g. recurrent deep venous thrombosis (DVT)
• Prior cortical or retinal stroke (diagnosed either clinically or by neuroimaging), or other prior cortical or retinal transient ischemic attack (TIA)
• Prior ipsilateral carotid endarterectomy
• Impaired renal function: estimated GFR \<40
• Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR)
• Mini Mental Status Exam score \< 24 (adjusted for age and education)
• Medical contraindication to MRI
• Pregnancy or women of child-bearing age who are not following an effective method of contraception
• Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound the neurological or functional outcome evaluations
• SBP \<90 or \> 200
• Known history of limb vascular disease, limb vascular bypass surgery, or limb deep venous thrombosis

Sponsors & Collaborators

• University of California, Los Angeles: lead
• American Heart Association: collaborator

Study Sites (1)

University of California Los Angeles UCLA

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Ischemic Stroke; Cerebral Small Vessel Diseases; Cognitive Dysfunction; Leukoencephalopathies; Leukoaraiosis

Interventions

Ischemic Preconditioning

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Investigative Techniques

Limitations and Caveats

We faced recruitment challenges over the course of the study. Many patients declined enrollment due to the 12-month time commitment of the study. We faced tolerability and compliance concerns with the few patients enrolled in the study. Despite our efforts, early termination of the trial led to small numbers of subjects analyzed.

Results Point of Contact

• Title: Latisha Sharma, MD
• Organization: University of California Los Angeles

lali@mednet.ucla.edu

310-794-6379

Study Officials

• Latisha K Sharma, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: June 23, 2014
• Study Start: November 1, 2015
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: March 10, 2021
• Results First Posted: March 10, 2021

Record last verified: 2021-03

Locations

US (1)