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

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Rochester, Minn. Mayo Clinic principal investigator Giuseppe Lanzino, M.D.	Open for enrollment	Contact information: Yeoniee Kim (507) 266-6585 Kim.Yeoniee@mayo.edu
Jacksonville, Fla. Mayo Clinic principal investigator Young Erben, M.D.	Open for enrollment	Contact information: Melissa Rompola CCRP (904) 953-4516 Rompola.Melissa@mayo.edu

Mayo Clinic Location

Status

Contact

Rochester, Minn.

Mayo Clinic principal investigator

Giuseppe Lanzino, M.D.

Open for enrollment

Contact information:

Yeoniee Kim

(507) 266-6585

Kim.Yeoniee@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Young Erben, M.D.

Open for enrollment

Contact information:

Melissa Rompola CCRP

(904) 953-4516

Rompola.Melissa@mayo.edu

More information

Publications

High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere. Read More on PubMed
For patients with asymptomatic high-grade carotid stenosis, clinical investigations have focused on preventing cerebral infarction, yet stenosis that reduces cerebral blood flow may independently impair cognition. Whether revascularization of a hemodynamically significant carotid stenosis can alter the course of cognitive decline has never been investigated in the context of a randomized clinical trial. Read More on PubMed

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