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Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H) (CREST-H)

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ClinicalTrials.gov Identifier: NCT03121209
Recruitment Status : Recruiting
First Posted : April 20, 2017
Last Update Posted : March 5, 2018
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Mayo Clinic
University of Alabama at Birmingham
University of Maryland
Information provided by (Responsible Party):
Randolph S. Marshall, Columbia University

Brief Summary:

We aim to determine whether cognitive impairment attributable to cerebral hemodynamic impairment in patients with high-grade asymptomatic carotid artery stenosis is reversible with restoration of flow. To accomplish this aim CREST-H will add on to the NINDS-sponsored CREST-2 trial (parallel, outcome-blinded Phase 3 clinical trials for patients with asymptomatic high-grade carotid artery stenosis which will compare carotid endarterectomy plus intensive medical management (IMM) versus IMM alone (n=1,240), and carotid artery stenting plus IMM versus IMM alone (n=1,240) to prevent stroke and death).

CREST-H addresses the intriguing question of whether cognitive impairment can be reversed when it arises from abnormal cerebral hemodynamic perfusion in a hemodynamically impaired subset of the CREST-2 -randomized patients. We will enroll 500 patients from CREST-2, all of whom receive cognitive assessments at baseline and yearly thereafter. We anticipate identifying 100 patients with hemodynamic impairment as measured by an inter-hemispheral MRI perfusion "time to peak" (TTP) delay on the side of stenosis. Among those who are found to be hemodynamically impaired and have baseline cognitive impairment, the cognitive batteries at baseline and at 1 year will determine if those with flow failure who are randomized to a revascularization arm in CREST-2 will have better cognitive outcomes than those in the medical-only arm compared with this treatment difference for those who have no flow failure.

We hypothesize that hemodynamically significant "asymptomatic" carotid disease may represent one of the few examples of treatable causes of cognitive impairment. If cognitive decline can be reversed in these patients, then we will have established a new indication for carotid revascularization independent of the risk of recurrent stroke.


Condition or disease
Internal Carotid Artery Stenosis Cognitive Impairment

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics
Actual Study Start Date : January 18, 2018
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022



Primary Outcome Measures :
  1. Change in cognitive score [ Time Frame: 1 year ]
    Among those with flow failure (PWI TTP>2 sec) and cognitive impairment (>1.0 SD below age-matched norms) at baseline, cognitive change at 1 year will be compared between those receiving revascularization (CEA or CAS) versus those receiving IMM alone in CREST-2. This treatment group difference in cognitive outcome will be compared with treatment group difference among patients with the same baseline cognitive impairment, but without flow failure at baseline. Primary outcome will be adjusted for age, baseline cognitive performance, depression, prior cerebral infarcts, subsequent silent infarction, WMH volume and microbleeds.


Secondary Outcome Measures :
  1. Silent infarcts [ Time Frame: 1 year ]
    MRI-determined silent infarcts present at 1 year that were not present at baseline, comparing by treatment group

  2. White matter hyperintensity (WMH) volume [ Time Frame: 1 year ]
    change in confluent white matter hyperintensity volume at 1 year, comparing by treatment group


Other Outcome Measures:
  1. Change in cognitive score at 2, 3, and 4 years [ Time Frame: 2-4 years ]
    Z-scored cognitive battery at 2, 3, and 4 years minus baseline, addressing the same comparisons as with the primary outcome at 1 year above.

  2. Correlation between change in cognition and change in perfusion [ Time Frame: 1 year ]
    Among those with baseline cognitive and hemodynamic impairment, degree of improvement in cognition will correlate with degree of improvement in TTP among those undergoing revascularization

  3. Use of alternative perfusion measures as criteria for Change in cognitive score at 1 year [ Time Frame: 1-4 years ]
    We will assess additional imaging markers including TTP delay >4sec, circle of willis collateral pattern, mean transit time, Tmax, CBF, and cerebral blood volume to determine if these have greater specificity for Z-scored cognitive battery change at 1-4 years



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Ages Eligible for Study:   35 Years to 86 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients enrolled in the parent study, CREST-2, will be eligible for participation in CREST-H.
Criteria

Inclusion Criteria:

  • Enrolled and randomized into CREST-2 (parent study)
  • Inclusion criteria for CREST-2
  • age 35-86

Exclusion Criteria (in addition to the exclusion criteria for CREST-2):

  • unable to undergo MRI (e.g. metal in body, pacemaker)
  • known allergy gadolinium contrast dye
  • pre-existing diagnosis of dementia
  • contralateral ICA stenosis >70% by MRA, CTA or Doppler ultrasound
  • history of severe head trauma
  • major depression
  • education less than 8 years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03121209


Contacts
Contact: Kevin Slane, BA 212-342-1152 kjs4@cumc.columbia.edu
Contact: Alberto Canaan, BA 212-342-1491 aac23@cumc.columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Randolph S Marshall, MD    212-305-8389    rsm2@columbia.edu   
Contact: Ryan D Lichtcsein    212-342-8658    rdl2116@columbia.edu   
Principal Investigator: Ronald M Lazar, PhD         
Principal Investigator: E Sander Connolly, MD         
Principal Investigator: David S Liebeskind, MD         
New York Presbyterian Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Jose Gutierrez, MD    212-305-1710    jg3233@cumc.columbia.edu   
Contact: Kevin J Slane, BA    2123421152    kjs4@cumc.columbia.edu   
Sponsors and Collaborators
Columbia University
National Institute of Neurological Disorders and Stroke (NINDS)
Mayo Clinic
University of Alabama at Birmingham
University of Maryland

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Randolph S. Marshall, Professor of Neurology, Columbia University
ClinicalTrials.gov Identifier: NCT03121209     History of Changes
Other Study ID Numbers: 1R01NS097876-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 20, 2017    Key Record Dates
Last Update Posted: March 5, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Constriction, Pathologic
Cognitive Dysfunction
Carotid Stenosis
Pathological Conditions, Anatomical
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases