Clinical trial NCT04219774: NeuroCognition After Carotid Recanalization
Official title: Neurocognitive Impairment Assessment in Symptomatic Carotid Occlusion Recanalized Endovascularly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cognition Disorder
Stroke
Occlusion Carotid
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2020-01-07
Enrollment: 25
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization, 1 non-randomized active comparator arm
Primary purpose: TREATMENT

Brief summary: Complete occlusion of the Internal carotid artery (ICA) by atherosclerotic disease (COICA) causes approximately 15%-25% of ischemic strokes in the carotid artery distribution. Patients treated with medical therapy have a 7%-10% risk of recurrent stroke per year for any stroke and a 5%-8% risk per year for ipsilateral ischemic stroke during the first 2 years after ICA occlusion. Internal carotid artery occlusion causes an estimated 61,000 first-ever strokes per year in the US an incidence more than twice the annual occurrence of ruptured intracranial aneurysms Additionally, 40% of subjects with COICA who present with transient ischemic attack (TIA) and 70% of COICA who present with stroke have cognitive decline with increased risk of vascular dementia and Alzheimer's' disease (AD) with time (2,3).

Symptomatic COICA subjects are at increased risk of developing cognitive impairment and progressive development of vascular dementia and AD with time. Our proposal leverages several compelling retrospective and prospective preliminary data from human to perform this exploratory trial with go/no-go criteria to proceed to a phase 3 based on the data generated

Detailed description: Study Design:

Prospective randomized open blinded end-point (PROBE) study

This is a phase 2 randomized single-center open label clinical trial with randomization of 1:1 to either best medical management vs. best medical management and endovascular revascularization of COICA.

Screening, Enrolling, \& Randomization:

All subjects who presents to our tertiary hospital with a diagnosis of COICA will undergo full evaluation including 1) documenting previous history of transient ischemic attack (TIA) and/or stroke; 2) cervical and brain CT angiography (CTA) to document complete occlusion; 3) CT perfusion (CTP) to assess for presence of penumbra evident by increased mean transient time (MTT) in the ipsilateral side of COICA; and 4) Montreal cognitive assessment (MoCA) score. If any subject is found to have complete occlusion of COICA, evident of abnormal/prolongation of MTT on CTP, previous history of TIA and or stroke, and MoCA \<26 or abnormal response on another neuropsychological assessment preformed in the screening battery, then further evaluation is obtained including: MRI spectroscopy to assess for presence/absence of lactate in the ipsilateral watershed area (centrum semiovale), and size of ipsilateral hippocampus and amygdala, additional cognitive testing battery, and digital subtraction angiography (DSA) to document adequately the type of COICA the subject have (type A-D).

If a subject meets all inclusion criteria (complete occlusion, MoCA \<26 and/or abnormal other neuropsychological test result, abnormal CTP) they will be randomized, after consent is obtained. If all inclusion criteria are met other than the CTP, they will be enrolled but not randomized. These subjects will only be eligible for best medical management- not surgical intervention.

If any subject does not have complete occlusion or abnormal MoCA \>26 or other neuropsychological assessment, then the subject is excluded and no further testing needed (see exclusion criteria).

If the subject meets all inclusion criteria, then a baseline of complete neurological testing, full demographics, CTA or MRA, CTP, MoCA, additional neurological testing, MRI spectroscopy and DSA are obtained and subject is randomized 1:1 to either best medical management or best medical management + endovascular balloon angioplasty and stenting. Follow up clinic visits are arranged at 6 and 12 months. Repeat testing of MoCA and additional cognitive testing battery are done at these clinical follow-up visits (6 and 12 months). MRI of the brain and is done at 6 and 12 months. DSA is performed at 1 year follow-up for intervention subjects to assess brain bio-markers and revascularization respectively.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 21
* Complete occlusion of cervical ICA on imaging studies (MRA or CTA) and confirmed with DSA
* History of TIA or stroke
* Increased MTT and/or time to peak (TTP) on CT perfusion as defined as T Max threshold of \> 10cc \> 4 seconds in the territory of the occluded carotid specifically in the MCA territory when compared to the opposite unaffected hemisphere (not required for observational cohort)
* All occlusion is due to atherosclerotic disease
* MoCA \< 26 or abnormal result on another test in the battery (abnormal defined as 1.5 SD below age/ gender/ education matched norms).
* Baseline MoCA assessed by the neurosurgery team or neuropsychology team
* Failed best medical treatment (defined below)
* Class A and B on COICA Classification
* Study team able to gain consent from subject or legal adult representative (LAR)

Exclusion Criteria:

* Non-atherosclerotic occlusive disease that may have caused the occlusion, including moyamoya, dissection, trauma or other causes
* Tandem occlusion
* No evidence of penumbra on CT perfusion
* Severe co-morbid diseases: Chronic Kidney Disease (CKD) stages 4 or 5, end-stage renal disease, liver cirrhosis; Chronic Obstructive Pulmonary Disease (COPD) requiring home oxygen; terminal illness such as cancer; Parkinson disease or other neurodegenerative diseases; severe congestive heart failure; seizures; debilitating stroke, Modified Rankin Score (mRS) ≥ 3
* Short life expectancy due to cancer or other co-morbid diseases
* Class D on COICA classification
* Normal neuropsychological battery test results
* Subject unwilling to randomized to surgical procedure
* Pregnant or risk of becoming pregnant

Primary outcomes:
measure: Change in Montreal Cognitive Assessment (MoCA) Score
timeFrame: Baseline, 6 months, 12 months
measure: Change in Composite Cognitive Score
timeFrame: Baseline, 6 months, 12 months
Secondary outcomes:
measure: Number of Participants With Stroke Within 30 Days Post Procedure
timeFrame: Up to 30 days post procedure
measure: Number of Participants With Intracranial Hemorrhage Within 72 Hours Post Procedure
timeFrame: Up to 72 hours post procedure
measure: Number of Participant Deaths
timeFrame: Up to 12 months
Other outcomes:
measure: Change in Mean Transit Time (MTT) on CT Perfusion
timeFrame: Baseline, 12 months
measure: Change in Size of Hippocampus
timeFrame: Baseline, 6 months, 12 months
measure: Change in Size of Amygdala
timeFrame: Baseline, 6 months, 12 months
measure: Number of Participants With the Presence of Lactate on 1H-MRI Spectroscopy
timeFrame: Baseline, 6 months, 12 months
Locations:
city: Iowa City
country: United States
facility: University of Iowa hospitals and Clinics
state: Iowa
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: David Hasan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zanaty M, Roa JA, Jabbour PM, Samaniego EA, Hasan DM. Recanalization of the Chronically Occluded Internal Carotid Artery: Review of the Literature. World Neurosurg X. 2019 Nov 21;5:100067. doi: 10.1016/j.wnsx.2019.100067. eCollection 2020 Jan.
citation: Hudson JS, Zanaty M, Wadman V, Nakagawa D, Ishii D, Roa JA, Al Kasabz S, Limaye K, Rossen JD, Jabbour P, Adams HP Jr, Samaniego EA, Hasan DM. Bradycardia and Asystole in Patients Undergoing Symptomatic Chronically Occluded Internal Carotid Artery Recanalization. World Neurosurg. 2019 Nov;131:e211-e217. doi: 10.1016/j.wneu.2019.07.125. Epub 2019 Jul 23.
citation: Limaye K, Zanaty M, Hudson J, Nakagawa D, Al Kasab S, Alvarez C, Dandapat S, Kung DK, Ortega-Gutierrez S, Jabbour P, Samaniego EA, Hasan D. The Safety and Efficacy of Continuous Tirofiban as a Monoantiplatelet Therapy in the Management of Ruptured Aneurysms Treated Using Stent-Assisted Coiling or Flow Diversion and Requiring Ventricular Drainage. Neurosurgery. 2019 Dec 1;85(6):E1037-E1042. doi: 10.1093/neuros/nyz226.
citation: Zanaty M, Howard S, Roa JA, Alvarez CM, Kung DK, McCarthy DJ, Samaniego EA, Nakagawa D, Starke RM, Limaye K, Al Kasab S, Chalouhi N, Jabbour P, Torner J, Tranel D, Hasan D. Cognitive and cerebral hemodynamic effects of endovascular recanalization of chronically occluded cervical internal carotid artery: single-center study and review of the literature. J Neurosurg. 2019 Mar 29;132(4):1158-1166. doi: 10.3171/2019.1.JNS183337. Print 2020 Apr 1.
citation: Zanaty M, Samaniego EA, Hasan DM. Letter to the Editor Regarding "Estimation and Recanalization of Chronic Occluded Internal Carotid Artery: Hybrid Operation by Carotid Endarterectomy and Endovascular Angioplasty". World Neurosurg. 2019 Jan;121:287. doi: 10.1016/j.wneu.2018.09.033. No abstract available.
citation: Zanaty M, Samaniego EA, Teferi N, Kung DK, Nakagawa D, Hudson J, Ortega-Gutierrez S, Allan L, Jabbour P, Hasan DM. Hybrid Surgery for Internal Carotid Artery Revascularization. World Neurosurg. 2019 Jan;121:137-144. doi: 10.1016/j.wneu.2018.09.230. Epub 2018 Oct 9.