- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03121209
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H) (CREST-H)
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics
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 385 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.
Study Overview
Status
Detailed Description
CREST-H sites will be drawn from actively-enrolling CREST-2 centers. The additional information obtained in CREST-H in this protocol will be the MR or CT imaging, which will be done at baseline for all patients enrolled in CREST-H, and at 1 year for those with hemodynamic impairment at baseline. The protocol will recommend an unblinded investigator at each CREST-H site who will order and obtain the study-related MRI sequences, upload de-identified image files to the CREST-2 central imaging site at U Maryland, and maintain blinding of the hemodynamic imaging data for their site (see Blinding below). Image analysis will be done at UCLA (for perfusion studies) and at Mayo Rochester for structural scans -- silent infarcts, WMH and microbleeds. Data management and statistical analysis will be done at UAB, which serves this role for CREST-2.
Cognitive Assessment.
CREST-H will use existing CREST-2 cognitive assessment infrastructure -- the Survey Research Unit at University of Alabama Birmingham. Added to the current CREST-2 battery is the Oral Trail Making A & B as an additional measure of executive function, which will be administered to every CREST-2 patient, regardless of their participation in CREST-H. Cognitive assessments in CREST-H must take place prior to revascularization or within two weeks after assignment to medical therapy alone. Testing in CREST-2 is repeated at 1 year, and every year thereafter up to 4 years. At each test interval, a composite (mean) Z-score is derived from published normative samples for each test outcome. The CREST-H primary outcome will be at 1 year in which the change in the composite Z-score from baseline will be calculated. Covariates will include age, education and depression. The test battery will be administered by a blinded assessor the same way for all CREST-2 and CREST-H enrolled patients. The cognitive domains being assessed in CREST-2/H are entirely consistent with those encompassed within the NINDS Common Data Elements (CDE).
Imaging protocol.
Multimodal MRI or CT perfusion imaging will be performed at baseline on every study subject.
Multimodal MRI, including routine parenchymal sequences and PWI utilizing dynamic susceptibility contrast technique, will be acquired at each participating CREST H site who have been approved for this imaging modality. CT perfusion, using iodinated contrast, will be used as an alternative PWI image for sites approved for this modality. Imaging will take place within 14 days after CREST-H enrollment and prior to any CREST 2 intervention for those randomized to CEA or CAS.
Standardized contrast agent injection protocol, appropriate preparation, and IV setup is used to ensure good scan quality. An antecubital vein IV catheter of 18-20 gauge is required. A test injection will be performed with approximately 10 ml of normal saline solution.
MRI image acquisition DWI/ADC (b=0, 1000 s/mm2 applied in each of three principal gradient directions), FLAIR, high-resolution T1, and GRE sequences will be acquired on 1.5-3.0 T scanners equipped with echo-planar imaging capability, using standard clinical protocols at participating CREST-H sites Total scanning time will be approximately 40 minutes. PWI acquisition protocol will be standardized across all CREST-H sites, using sequential T2*-weighted (gradient echo) EPI time sequence scanning. A modified 2-phase contrast injection scheme will be used to perform CEMRA and DSC perfusion imaging, without need for additional contrast.
CT perfusion imaging will follow the protocol outlined in the updated Imaging MOP for CREST-H. The CT perfusion study is identical to the clinical CTP protocol used for acute stroke imaging in most institutions.
Perfusion imaging analysis.
PWI source images will be sent to the core laboratory at UCLA and processed with the OleaSphere software platform, using deconvolution of tissue and arterial signals in an expedited manner, yielding standardized data regardless of the acquisition system at each site. Hemodynamic impairment is defined as TTP >1.25 sec in the middle cerebral artery and anterior cerebral artery territories of the ipsilateral hemisphere to the carotid lesion compared with the same territory in the opposite hemisphere. Longitudinal analyses will investigate the change in the TTP >1.25 sec lesion at 1 year comparing the revascularization versus the medical only arm. Continuous values for this volumetric change will be used to calculate the correlation between degree of cognitive change and degree of perfusion change. The continuous Tmax variable, as well as standard perfusion parameters of CBV, CBF Tmax, and MTT will be analyzed on the serial imaging studies in each case with MR imaging. Co-registered, voxel-based changes in serial perfusion values will also be explored with multiparametric (e.g. CBV, CBF, Tmax, MTT) values.
Image de-identification and blinding.
All MR or CT image files will be de-identified under the supervision of an unblinded Investigator (UI) at each institution and uploaded to the CREST-2 Imaging Core site at U Maryland. In order to assure that the PWI scan information from CREST-H does not compromise the integrity of the parent trial, the results of the perfusion scan will be blinded to the investigator team.
Image transfer.
Participating sites will utilize the same file transfer protocol (ftp) to transfer images to U Maryland for CREST-H as is already established for CREST-2. The images will be stored in a HIPAA-compliant, firewall protected server within the U Maryland archival system. A CREST-2 dedicated ftp linkage between the VIC at U Maryland and UCLA; and the VIC at U Maryland and Mayo-Rochester will be utilized to make each perfusion image file available for download by UCLA (Liebeskind lab) and each structural image (DWI, FLAIR, GRE) by Mayo-Rochester (Huston lab).
MRI structural analysis.
Structural MRI analysis at Mayo-Rochester will utilize NIH NINDS Common Data Elements developed for the CREST-2 grant. The following definitions apply:
- silent infarct --- non-confluent hyperintense lesion >1mm on FLAIR sequence on 1-year MRI not present on baseline FLAIR MRI.
- Cerebral microbleed - hypointense 1-2mm non-confluent lesion on baseline GRE sequence.
- WMH volume -- White matter hyperintensity volume refers to confluent periventricular high intensity lesions on FLAIR imaging, and will be derived using an automated T2 WMH quantification at the Huston lab.
Data from image analysis (TTP delay, WMHV, silent infarct count, microbleed count) performed at UCLA and Mayo-Rochester will be entered electronically on CREST-H data forms via the CREST-2 SDCC website at UAB, where it will be stored on a separate webpage linked to the rest of the CREST-2 data, including baseline and yearly cognitive assessments. The electronic data entry system (eDES) for CREST-2 is a mature system, successfully reviewed by FDA audit in other studies, providing standard approaches for entry-confirmation-locking of data forms, and supporting range and validity checking for data provided.
. Analysis.
Specific Aim 1. To determine whether cognition can be improved by revascularization among a subset of CREST-2 patients with hemodynamic impairment at baseline.
The primary hypothesis is to assess if the magnitude of the treatment differences (revascularization versus medical management alone) differs between those with flow failure compared to those without flow failure using the Z-scored cognitive outcomes (C0, C(1). That is, the primary hypothesis is an interaction hypothesis that will be assessed using linear regression, specifically: (C1 - C0) = β0 + β1T + β2F + β3TF + β4C0 + (other covariates), where C1 is the cognitive z-score at year 1, C0 the cognitive z-score at baseline, T the treatment indicator variable, F the flow failure indicator variable, and βi the regression parameters to be estimated. The parameter of interest for the primary hypothesis is then β3 that would assess if the magnitude of treatment difference in the change in cognitive score between baseline and 1-year is similar for those with versus without flow failure.
Secondary Aims: To determine if the number of silent infarcts and white matter hyperintensity volume at 1 year is different between the revascularization and the medical-only arms.
For the secondary aims we will calculate the number of new silent cerebral infarctions occurring over the first year, and the change in the WMH volume. The approach for analysis of the number of new silent infarcts will depend on the average number and distribution of the number of new infarcts. The analytic approach will be linear regression if the number of new infarcts is large (considered more likely the case), or Poisson Regression if the number is smaller (considered less likely the case). The analysis of the change in WMH will use a linear regression approach.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Kevin Slane, BA
- Phone Number: 212-342-1152
- Email: kjs4@cumc.columbia.edu
Study Locations
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 1M9
- Recruiting
- Vancouver General Hospital
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Contact:
- Genoveva Maclean,, BA, BSN, RN
- Phone Number: 604-875-4554
- Email: genoveva@bcstrokecentre.ca
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Principal Investigator:
- Philip Teal, M.D.
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Manitoba
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Winnipeg, Manitoba, Canada, MB R2H 2A6
- Recruiting
- St. Boniface Hospital
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Contact:
- Wendy Weighell
- Phone Number: 204-235-3916
- Email: wweighell@sbgh.mb.ca
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Principal Investigator:
- Randolph Guzman, M.D.
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Alabama
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Birmingham, Alabama, United States, 35294
- Recruiting
- The University of Alabama at Birmingham
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Contact:
- Rhonda Whidden
- Phone Number: 205-934-2918
- Email: rwhidden@uabmc.edu
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Principal Investigator:
- Veeranjaneyulu Prattipati, M.D.
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Huntsville, Alabama, United States, 35801
- Recruiting
- Huntsville Hospital/ Heart Center Research Alabama
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Contact:
- Weston Smith
- Phone Number: 256-698-0405
- Email: wsmith@hsvheartmds.com
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Principal Investigator:
- Warren Strickland, M.D.
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Arizona
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Phoenix, Arizona, United States, 85013
- Recruiting
- St. Joseph's Hospital and Medical Center/ Barrow
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Contact:
- Steev Mallon
- Phone Number: 602-406-4217
- Email: steev.mallon2@DignityHealth.org
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Principal Investigator:
- Andrew Ducruet, M.D.
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Tucson, Arizona, United States, 85724
- Not yet recruiting
- University of Arizona
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Contact:
- Joshua Black
- Phone Number: 520-626-3576
- Email: joshuablack@email.arizona.edu
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Principal Investigator:
- Wei Zhou, MD, FACS
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Arkansas
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Little Rock, Arkansas, United States, 72143
- Recruiting
- Central Arkansas Veteran's Healthcare System
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Contact:
- Sandi Brock, RN
- Phone Number: 501-257-6906
- Email: sjbrock@uams.edu
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Principal Investigator:
- Mohammed Moursi, M.D.
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California
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Los Angeles, California, United States, 90027
- Recruiting
- Kaiser Permanente Los Angeles Medical Center
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Contact:
- Vena Sobhawongse
- Phone Number: 323-783-3093
- Email: Vena.S.Sobhawongse@kp.org
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Principal Investigator:
- Navdeep Sangha, M.D.
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Los Angeles, California, United States, 90033
- Recruiting
- Keck Medical Center of University of Southern California
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Contact:
- Clare Binley
- Phone Number: 323-442-5710
- Email: Clare.Binley@med.usc.edu
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Principal Investigator:
- Sebina Bulic, M.D.
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Los Angeles, California, United States, 90095
- Recruiting
- University of California at Los Angeles
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Contact:
- Gabriela Flores
- Phone Number: 310-206-1115
- Email: GabrielaFlores@mednet.ucla.edu
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Principal Investigator:
- Wesley S. Moore, M.D.
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San Diego, California, United States, 92123
- Recruiting
- Kaiser Permanente
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Contact:
- Stephanie Martinez
- Phone Number: 858-266-6602
- Email: stephanie.m1.martinez@kp.org
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Principal Investigator:
- Edward Plecha, MD
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San Diego, California, United States, 92182
- Recruiting
- University Of California San Diego
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Contact:
- Peter Chase
- Email: pchase@health.ucsd.edu
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Principal Investigator:
- Alexander A Khalessi, MD
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San Francisco, California, United States, 94121
- Recruiting
- San Francisco VA Medical Center
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Contact:
- Sandra Perez
- Phone Number: 22697 415-221-4810
- Email: sandra.perez@va.gov
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Principal Investigator:
- Joseph Rapp, M.D.
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Stanford, California, United States, 94305
- Recruiting
- Stanford University Medical Center
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Contact:
- Guiping Qin
- Phone Number: 650-721-5329
- Email: gqin68@stanford.edu
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Principal Investigator:
- Gary Steinberg, M.D.
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Connecticut
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New Haven, Connecticut, United States, 06520
- Recruiting
- Yale New Haven Hospital
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Contact:
- Jackie Gamberdella
- Phone Number: 203-737-1899
- Email: Jacqueline.Gamberdella@yale.edu
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Principal Investigator:
- Carlos Mena-Hurtado, M.D.
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Florida
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Clearwater, Florida, United States, 33756
- Recruiting
- Morton Plant Hospital
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Contact:
- Shawna Miller
- Phone Number: 727-461-8885
- Email: shawna.miller@baycare.org
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Principal Investigator:
- Eric Lopez del Valle, M.D.
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Gainesville, Florida, United States, 32610
- Recruiting
- University of Florida Health at Shands
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Contact:
- Teresa Lyles
- Phone Number: 352-294-5693
- Email: Teresa.Lyles@neurology.ufl.edu
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Principal Investigator:
- Anna Khanna, M.D.
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Jacksonville, Florida, United States, 322224
- Recruiting
- Mayo Clinic Florida
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Contact:
- Alexandra Kropnick
- Phone Number: 904-953-2077
- Email: Kropnick.Alexandra@mayo.edu
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Principal Investigator:
- Albert Hakaim, M.D.
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Miami, Florida, United States, 33136
- Recruiting
- University of Miami Hospital
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Contact:
- Andrea Escobar, MPH
- Phone Number: 305-243-8876
- Email: aescobar@med.miami.edu
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Principal Investigator:
- Amer Malik, M.D.
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Illinois
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Chicago, Illinois, United States, 60637
- Recruiting
- University of Chicago
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Contact:
- Cedric McKoy, MSN, ACNP
- Phone Number: 773-702-7215
- Email: jbrorson@neurology.bsd.uchicago.edu
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Principal Investigator:
- James Brorson, M.D.
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Evanston, Illinois, United States, 60208
- Recruiting
- Northwestern University
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Contact:
- Ayesha Muzaffar
- Phone Number: 312-926-4251
- Email: ayesha.muzaffar@northwestern.edu
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Principal Investigator:
- Sameer Ali, M.D.
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Rockford, Illinois, United States, 61114
- Recruiting
- Mercy Health Riverside
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Principal Investigator:
- Vibhav Bansal, MD
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Contact:
- Nicole Morud, DNP RN
- Phone Number: 815-971-1877
- Email: nmorud@mhemail.org
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Iowa
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Iowa City, Iowa, United States, 52242
- Recruiting
- University of Iowa
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Contact:
- Judith Pena-Quevedo
- Phone Number: 319-353-8736
- Email: judith-pena-quevedo@uiowa.edu
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Principal Investigator:
- Mel Sharafuddin, M.D.
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Louisiana
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New Orleans, Louisiana, United States, 70121
- Recruiting
- Ochsner Health System
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Contact:
- Shannon Williams
- Phone Number: 504-842-6487
- Email: slwilliams@ochsner.org
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Principal Investigator:
- Charles Sternbergh III, M.D.
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Maine
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Portland, Maine, United States, 04102
- Recruiting
- Maine Medical Center
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Contact:
- Debbie Cushing
- Phone Number: 207-885-4438
- Email: cushid@mmc.org
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Principal Investigator:
- Robert Ecker, M.D.
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Maryland
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Baltimore, Maryland, United States, 21201
- Recruiting
- University of Maryland VA
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Principal Investigator:
- Shahab Toursavadkohi, M.D.
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Contact:
- Dawn Barth
- Email: DBarth@som.umaryland.edu
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Gaithersburg, Maryland, United States, 20878
- Recruiting
- Adventist HealthCare/White Oak Medical Center
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Contact:
- Tamika Magee
- Phone Number: 301-891-5493
- Email: tmagee@adventisthealthcare.com
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Principal Investigator:
- Fayaz Shawl, M.D.
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Michigan
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Flint, Michigan, United States, 48532
- Recruiting
- Michigan Vascular Center/McLaren-Flint
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Contact:
- Maureen Blewett
- Phone Number: 810-600-2009
- Email: maureena@michiganvascular.com
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Principal Investigator:
- Robert Molnar, M.D.
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Recruiting
- University of Minnesota
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Contact:
- Amanda Weller
- Phone Number: 612-301-1593
- Email: andv0003@umn.edu
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Principal Investigator:
- Andy Grande, M.D.
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Rochester, Minnesota, United States, 55905
- Recruiting
- Mayo Clinic Rochester
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Contact:
- Yeoniee Kim
- Phone Number: 507-293-1963
- Email: Kim.Yeoniee@mayo.edu
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Principal Investigator:
- Giuseppe Lanzino, M.D.
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Missouri
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Saint Louis, Missouri, United States, 63141
- Recruiting
- Mercy Hospital St Louis
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Contact:
- Jessica Schulte
- Phone Number: 314-251-5916
- Email: Jessica.Schulte@Mercy.Net
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Principal Investigator:
- Scott Westfall, M.D.
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New York
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Buffalo, New York, United States, 14203
- Recruiting
- SUNY Buffalo
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Contact:
- Mary Hartney
- Phone Number: 716-888-4812
- Email: mhartney@ubns.com
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Principal Investigator:
- Adnan Siddiqui, MD, PhD
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New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Center
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Contact:
- Randolph S Marshall, MD
- Phone Number: 212-305-8389
- Email: rsm2@columbia.edu
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Contact:
- Ryan D Lichtcsein
- Phone Number: 212-342-8658
- Email: rdl2116@columbia.edu
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Principal Investigator:
- Ronald M Lazar, PhD
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Principal Investigator:
- E Sander Connolly, MD
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Principal Investigator:
- David S Liebeskind, MD
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New York, New York, United States, 10065
- Recruiting
- Weill Cornell Medical Center
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Contact:
- Carla Sherman
- Phone Number: 212-746-6757
- Email: cas9149@med.cornell.edu
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Principal Investigator:
- Dana Leifer, MD
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New York, New York, United States, 10032
- Recruiting
- New York Presbyterian Columbia University Medical Center
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Contact:
- Jose Gutierrez, MD
- Phone Number: 212-305-1710
- Email: jg3233@cumc.columbia.edu
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Contact:
- Kevin J Slane, BA
- Phone Number: 2123421152
- Email: kjs4@cumc.columbia.edu
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Recruiting
- Wake Forest University Health Sciences
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Contact:
- Krystal Schmidt
- Phone Number: 336-716-9603
- Email: kschmidt@wakehealth.edu
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Principal Investigator:
- Cheryl Bushnell, M.D.
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Winston-Salem, North Carolina, United States, 27103
- Recruiting
- Novant Health Forsythe
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Contact:
- Olga Dubangiu
- Phone Number: 336-718-5871
- Email: odubangiu@novanthealth.org
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Principal Investigator:
- Donald Heck, MD
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Ohio
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Cleveland, Ohio, United States, 44106
- Recruiting
- University Hospitals Cleveland Medical Center
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Contact:
- Linette Mercer, BSN RN
- Phone Number: 216-844-3013
- Email: Linette.Mercer@UHhospitals.org
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Principal Investigator:
- Norman H Kumins, M.D.
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Cleveland, Ohio, United States, 44106
- Recruiting
- Louis Stokes Cleveland VA Medical Center
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Contact:
- Lisa Tucker
- Phone Number: 3595 216-791-3800
- Email: lisa.tucker@va.gov
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Principal Investigator:
- Svetlana Pundik, M.D.
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Columbus, Ohio, United States, 43210
- Recruiting
- Ohio State Medical Center
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Contact:
- Roderick Liptrot
- Phone Number: 614-293-8536
- Email: Roderick.Liptrot@osumc.edu
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Principal Investigator:
- Jean Starr, M.D.
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Columbus, Ohio, United States, 43214,
- Recruiting
- Ohio Health Research Institute
-
Contact:
- Amanda Bliemeister
- Phone Number: 614-566-1268
- Email: Amanda.Bliemeister@OhioHealth.com
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Principal Investigator:
- Gary Ansel, M.D.
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Pennsylvania
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Altoona, Pennsylvania, United States, 16601
- Recruiting
- UPMC Altoona
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Principal Investigator:
- Cynthia Kenmuir, MD
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Contact:
- Jason Weimer
- Email: weimerjm@upmc.edu
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Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- Hospital of the University of Pennsylvania
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Contact:
- Nichole Gallatti
- Phone Number: 215-349-8651
- Email: nichole.gallatti@uphs.upenn.edu
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Principal Investigator:
- Michael Mullen, M.D.
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Pittsburgh, Pennsylvania, United States, 15213
- Recruiting
- UPMC Presbyterian University Hospital
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Contact:
- Cathy Van Every
- Phone Number: 412-647-7099
- Email: vaneverycc@upmc.edu
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Principal Investigator:
- Marcelo Rocha, M.D.
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Rhode Island
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Providence, Rhode Island, United States, 02906
- Recruiting
- The Miriam Hospital/ Rhode Island Hospital
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Contact:
- Wendy Smith
- Phone Number: 401-793-4105
- Email: WSmith@Lifespan.org
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Principal Investigator:
- Gaurav Jindal, M.D.
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South Carolina
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Charleston, South Carolina, United States, 29425
- Recruiting
- Medical University of South Carolina
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Contact:
- Vicki Streets
- Phone Number: 814-490-7034
- Email: streetsv@musc.edu
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Principal Investigator:
- Christine Holmstedt, M.D.
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South Dakota
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Sioux Falls, South Dakota, United States, 57108
- Recruiting
- North Central Heart Institute
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Contact:
- Patty Eisenbraun
- Phone Number: 605-977-5336
- Email: peisenbraun@ncheart.com
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Principal Investigator:
- Michael Bacharach, M.D.
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Tennessee
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Knoxville, Tennessee, United States, 37934
- Recruiting
- Tennova Healthcare/ Turkey Creek Medical Center
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Contact:
- Nancy Bradley, RN, CCRC
- Phone Number: 865-218-7538
- Email: nancy.bradley@tennova.com
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Principal Investigator:
- Malcolm Foster, M.D.
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Texas
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Houston, Texas, United States, 77030
- Recruiting
- Houston Methodist Hospital
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Contact:
- Jason Lee
- Phone Number: 832-236-9396
- Email: jlee5@houstonmethodist.org
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Principal Investigator:
- David Chiu, M.D.
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Utah
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Salt Lake City, Utah, United States, 84132
- Recruiting
- University of Utah Hospitals and Clinics
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Principal Investigator:
- Jennifer Majersik, M.D.
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Contact:
- Kinga Aitken
- Phone Number: 801-581-5523
- Email: kinga.aitken@hsc.utah.edu
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Virginia
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Charlottesville, Virginia, United States, 22908
- Recruiting
- University of Virginia Health System
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Contact:
- Caryn Wolf
- Phone Number: 434-924-9271
- Email: CLW8PV@hscmail.mcc.virginia.edu
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Principal Investigator:
- Avery Evans, M.D.
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Falls Church, Virginia, United States, 22042
- Recruiting
- Inova Fairfax Health Care
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Contact:
- Renee Mercier
- Phone Number: 703-776-8425
- Email: Renee.Mercier@inova.org
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Principal Investigator:
- Dipankar Mukherjee, M.D.
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Washington
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Seattle, Washington, United States, 98108
- Recruiting
- VA Puget Sound Health Care System
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Contact:
- Susan Bigda
- Phone Number: 206-277-4681
- Email: susan.bigda@va.gov
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Principal Investigator:
- Gale Tang, M.D.
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Seattle, Washington, United States, 98104
- Recruiting
- University of Washington Medicine-Harborview Medical Center
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Contact:
- Hope Clark-Bell
- Phone Number: 206-744-9457
- Email: Hoper555@uw.edu
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Principal Investigator:
- David Tirschwell, M.D.
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Wisconsin
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La Crosse, Wisconsin, United States, 54601
- Recruiting
- Gundersen Clinic, Ltd
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Contact:
- Sara Meyers
- Phone Number: 608-775-0238
- Email: srmeyers@gundersenhealth.org
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Principal Investigator:
- Clark Davis, M.D.
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Madison, Wisconsin, United States, 53792
- Recruiting
- University of Wisconsin Hospital and Clinics
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Contact:
- Bridget Johnson
- Phone Number: 608-265-4420
- Email: johnsonbri@surgery.wisc.edu
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Principal Investigator:
- Girma Tefera, M.D.
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
---|
Revascularization Arm (CEA or CAS)
These patients will have been randomized (via the parent trial, CREST-2) to receive intensive medical management as well as either Carotid Endarterectomy (CEA--if they are in the parent study Surgical trial) or Carotid Artery Stenting (CAS--if they are in the parent study Stenting trial).
|
Intensive Medical Management (IMM) Arm
These patients will have been randomized (via the parent trial, CREST-2) to receive medical management only, which includes aspirin.
high dose cholesterol lowering agent to a target LDL<70, intensive blood pressure management to target <130/80, smoking cessation, and diabetic control.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in cognitive score
Time Frame: 1 year
|
Among those with flow failure (PWI TTP>1.25 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.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Silent infarcts
Time Frame: 1 year
|
MRI-determined silent infarcts present at 1 year that were not present at baseline, comparing by treatment group
|
1 year
|
White matter hyperintensity (WMH) volume
Time Frame: 1 year
|
change in confluent white matter hyperintensity volume at 1 year, comparing by treatment group
|
1 year
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
2-4 years
|
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
|
1 year
|
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
|
1-4 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Randolph S Marshall, MD, Columbia University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AAAR5617
- 1R01NS097876-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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