Clinical trial NCT04916210: Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY
Official title: Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Stroke
Intracerebral Hemorrhage
Subarachnoid Hemorrhage
Dementia, Vascular
Mild Cognitive Impairment
Vascular Cognitive Impairment
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2021-06-07
Enrollment: 8000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with recent (≤ 6 weeks) acute ischemic stroke, intracerebral hemorrhage or aneurysmal subarachnoid hemorrhage and no history of dementia.

Brief summary: The overall goal of the DISCOVERY study is to better understand what factors contribute to changes in cognitive (i.e., thinking and memory) abilities in patients who experienced a stroke. The purpose of the study is to help doctors identify patients at risk for dementia (decline in memory, thinking and other mental abilities that significantly affects daily functioning) after their stroke so that future treatments may be developed to improve outcomes in stroke patients. For this study, a "stroke" is defined as either (1) an acute ischemic stroke (AIS, or blood clot in the brain), (2) an intracerebral hemorrhage (ICH, or bleeding in the brain), (3) or an aneurysmal subarachnoid hemorrhage (aSAH, or bleeding around the brain caused by an abnormal bulge in a blood vessel that bursts).

The investigators hypothesize that:

1. The size, type and location of the stroke play an important role in recovery of thinking and memory abilities after stroke, and pre-existing indicators of brain health further determine the extent of this recovery.
2. Specific stroke events occurring in individuals with underlying genetic or biological risk factors can cause further declines in brain heath, leading to changes in thinking and memory abilities after stroke.
3. Studying thinking and memory alongside brain imaging and blood samples in patients who have had a stroke allows for earlier identification of declining brain health and development of individualized treatment plans to improve patient outcomes in the future.

Detailed description: This is a prospective, multi-center, observational, nested-cohort study. A total of 8,000 patients hospitalized at the DISCOVERY clinical sites with acute-onset AIS, ICH or aSAH and no history of dementia will be enrolled.

All participants will undergo baseline screening for evidence of pre-stroke dementia. Those who pass baseline screening will complete a blood draw and a series of cognitive and functional assessments at baseline.

Participants will undergo in-person (3-6 months, 18 months) and telephone (annual) follow-up visits for the duration of the study to assess for longitudinal cognitive and functional outcomes. In addition to Tier 1 procedures, at each in-person follow-up visit, Tier 2 participants will also undergo brain MRI scanning, comprehensive cognitive assessment batteries and longitudinal blood collection; and Tier 3 participants will also complete a specialized imaging of the brain (amyloid- and tau-PET/CT scans), which is intended to identify special biomarkers of dementia.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years
2. Admitted to the hospital with a diagnosis of acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), or aneurysmal subarachnoid hemorrhage (aSAH)
3. Radiographic confirmatory evidence of: (1) AIS (based on a focal area of restricted diffusion on MRI), (2) non-traumatic ICH (based on evidence of acute parenchymal hemorrhage CT or brain MRI) or (3) non-traumatic acute aSAH (based on evidence of subarachnoid hemorrhage on CT or MRI and evidence of aneurysm on CT angiography, MR angiography, or conventional catheter-based angiography)
4. Able to complete baseline visit in person or by phone within 6 weeks of stroke onset
5. Able to provide informed consent by self or proxy
6. Fluent in English or Spanish prior to stroke onset

Exclusion Criteria:

1. Documented history of pre-stroke dementia or fails dementia pre-screen
2. Concurrently enrolled into a study that is not approved under the DISCOVERY Co-Enrollment Policy
3. Unable to complete study protocol (advanced directives such as comfort measures only, or inability to complete the study due to severe medical/behavioral co-morbidities), as determined by physician investigator during screening process

   Additional exclusion criteria for Tier 2 participants:
4. Contraindication to MRI: presence of electrically, magnetically, or mechanically activated implants (such as cardiac pacemakers, cochlear implants, implanted pumps); or metallic clips in the brain

   Additional exclusion criteria for Tier 3 participants:
5. Age \<50 years
6. Biologically female individuals who are pregnant or seeking to become pregnant
7. Known to have one of the following genetic conditions which can increase the risk of developing cancer: Cowden disease, Lynch syndrome, hypogammaglobulinemia, Wiskott-Aldrich syndrome, Down's syndrome.

Primary outcomes:
measure: Change in post-stroke cognitive impairment and dementia (PSCID) diagnosis status
timeFrame: Baseline to 48 months post-index stroke
Secondary outcomes:
measure: Change in cognitive function
timeFrame: Baseline to 3-6, 12, 18, 24, 36 and 48 months post-index stroke
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Health
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: The Hospital of the University of Pennsylvania
state: Pennsylvania
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Houston
country: United States
facility: UTHealth
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington, Harborview Medical Center
state: Washington
Study officials:
affiliation: Massachusetts General Hospital
name: Natalia Rost, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Steven Greenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: