Clinical trial NCT06284213: Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia Consortium
Official title: Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia Consortium
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cognitive Impairment
Dementia
Keywords: Biomarkers
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Duke University
name: Johns Hopkins University
name: University of New Mexico
name: University of Southern California
name: University of Kentucky
name: Rush University Medical Center
name: University of Maryland, Baltimore
name: University of California, San Francisco
name: University of California, Los Angeles
name: University of California, Davis
name: University of Texas
name: The University of Texas Health Science Center at San Antonio
name: The University of Texas Health Science Center, Houston
name: Mayo Clinic
name: University of Mississippi Medical Center
name: Washington University School of Medicine
name: Olive View-UCLA Education & Research Institute
First posted: 2024-02-28
Enrollment: 1892
Sex: ALL
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be selected from a variety of sources across the MarkVCID Consortium sites. These sources include, but are not limited to:

* MarkVCID1 or other research studies
* Alzheimer's Disease Research Center database
* Patient registries such as Volunteer for Health
* Community centers or organizations
* Clinics:

  * Primary care
  * Neurology
  * Stroke Center
  * Outpatient Diabetes
  * Memory \& Aging

Brief summary: Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID) is an NIH-funded consortium dedicated to finding biomarkers involved in age-related thinking and memory problems. Alzheimer's disease and other dementias leave signatures on brain scans or in the blood called biomarkers. The MarkVCID study will measure a panel of candidate biomarkers in 1800 participants and watch them closely to see what they tell us about changes in brain function and risk of memory loss.

Age-related problems in thinking and memory represent some of the greatest risks to public health in the US and globally. Diseases that affect small blood vessels in the brain have been shown to be major contributors to these changes. However, research and patient care can be held back by limited biomarkers that identify who should be treated.

The MarkVCID Consortium includes 17 US medical centers, a Coordinating Center, an External Advisory Committee, and NIH leadership. Data and biospecimens collected as part of this research study will be stored in a research database and biorepositories, so that researchers can use this information to study brain function.

Detailed description: Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID) is an NIH-funded multisite consortium dedicated to developing promising predictive, diagnostic, target engagement and progression candidate biomarkers of small vessel disease in VCID. MarkVCID is a collaborative consortium of nine North American research sites (consisting of 17 institutions nationwide), a Coordinating Center, External Advisory Committee, and NIH leadership.

MGH serves as the Consortium's Coordinating Center and is comprised of an administrative and data core providing participating research sites with a common support infrastructure that facilitates cross-site collaborations, oversees development of standard operating procedures and data collection methods and manages consortium-wide data.

In phase two of the MarkVCID study, research sites are charged with enrolling and following ≥200 diverse human subjects with cognitive complaints and/or early symptomatic stages of cognitive impairment and dementia potentially associated with cerebrovascular small vessel disease. Sites will share data with the Coordinating Center which will be used for validation studies of chosen consortium biomarkers. Throughout the duration of the study, sites will utilize harmonized procedures and data collection methods to engage in multi-site biomarker validation. Both Cores comply with regulations for the protection of human research subjects (including Good Clinical Practices (GCP), 21 Code of Federal Regulations (CFR)) and with the International Conference on Harmonization (ICH) Regulations E2A and E6.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 60 and ≤ 90 years
* Diagnosis of normal cognition with at least one criterion for vascular risk\*, subjective cognitive decline (preliminary diagnosis based on self-report question or eCog-12), mild cognitive impairment, or mild dementia based on standard research criteria
* Fluent in English or Spanish
* No contraindications to MRI including CVR
* No confounding neurologic, psychiatric, or medical disease

  \*Participants with normal cognition must meet at least one criterion (diabetes, OR hypertension plus, OR MRI factors) for vascular risk prior to enrollment:
* Diabetes (at least one of the following):

  * Fasting (8-hour fast, usually overnight) blood sugar ≥126 mg/dL (≥7 mmol/L, or ≥1260 mg/L)
  * Random or Post-prandial blood sugar ≥200 mg/dL (≥11.11 mmol/L, or ≥2000 mg/L)
  * HbA1C ≥6.5% (or ≥47.5412 mmol/mol)
  * Treatment with an anti-diabetic medicine
* Hypertension plus (at least two of the following):

  * Use of anti-hypertensive medications for lowering blood pressure for ≥ 10 years
  * Current use of two or more anti-hypertensive medications for lowering blood pressure
  * One measured blood pressure in a research or clinical setting in the last 2 years with SBP ≥140 or DBP ≥90
  * A second measured blood pressure in a research or clinical setting on a different date in the last 2 years with SBP ≥140 or DBP ≥90
  * Evidence of likely HTN end-organ damage (e.g., LVH, albuminuria, eGFR\<60, CHF)
* MRI factors (at least one of the following):

  * Peri-Ventricular Fazekas Extent Grade or Deep Fazekas Extent Grade ≥ 2
  * 1 or more microbleeds
  * 1 or more lacunar infarcts

Exclusion Criteria:

* Neurologic Disease: Based on the available data and investigator's impression, exclude those with confounding neurologic disease that would interfere with test performance or with biomarker analysis:

  * Frontotemporal lobar degeneration (FTLD)
  * Lewy body dementia (LBD)
  * Parkinson's disease
  * Multi system atrophy
  * Traumatic brain injury (TBI)-related cognitive impairment
  * TBI that interferes with MRI biomarker analyses (e.g., large volume traumatic lesion)
  * Non-small vessel strokes that interfere with test performance (e.g., post-stroke cognitive impairment or aphasia)
  * Non-small vessel strokes that interfere with MRI biomarker analysis (e.g., large volume strokes)
  * CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
  * Individuals known to be receiving, or planning to receive, anti-amyloid immunotherapy\*
  * Other neurologic conditions that interfere with test performance or biomarker analysis

    * Individuals prescribed anti-amyloid immunotherapy after MarkVCID enrollment should be kept in the study.
* Medical and Psychiatric Conditions: Exclude those with medical and psychiatric conditions that would confound the course or interfere with test performance:

  * Schizophrenia or other active/severe psychotic disorders
  * Medical or psychiatric conditions likely to interfere with participation or retention (e.g., metastatic or malignant CNS cancer, active/severe depression or anxiety, HIV- Associated Neurocognitive Disorder)
  * Contraindications to MRI procedures, such as:

    * Claustrophobia
    * Cardiac pacemaker
    * Intracranial clips/metal implants
  * Contraindications to CVR:

    * COPD or other respiratory condition requiring oxygen therapy
    * Asthma or other respiratory condition requiring current use of medications such as inhalers

Primary outcomes:
measure: SVD progression as measured by decline in global cognition
timeFrame: The cognitive battery is implemented, and global cognition calculated, at Baseline and Years 1, 2 and 3 post-baseline.
Secondary outcomes:
measure: SVD progression as measured by decline in executive function
timeFrame: The cognitive battery is implemented, and executive function calculated, at Baseline and Years 1, 2 and 3 post-baseline.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Medical Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center & Illinois Institute of Technology
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
Study officials:
affiliation: Massachusetts General Hospital
name: Steven M. Greenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Besser L, Kukull W, Knopman DS, Chui H, Galasko D, Weintraub S, Jicha G, Carlsson C, Burns J, Quinn J, Sweet RA, Rascovsky K, Teylan M, Beekly D, Thomas G, Bollenbeck M, Monsell S, Mock C, Zhou XH, Thomas N, Robichaud E, Dean M, Hubbard J, Jacka M, Schwabe-Fry K, Wu J, Phelps C, Morris JC; Neuropsychology Work Group, Directors, and Clinical Core leaders of the National Institute on Aging-funded US Alzheimer's Disease Centers. Version 3 of the National Alzheimer's Coordinating Center's Uniform Data Set. Alzheimer Dis Assoc Disord. 2018 Oct-Dec;32(4):351-358. doi: 10.1097/WAD.0000000000000279.
citation: Staffaroni AM, Asken BM, Casaletto KB, Fonseca C, You M, Rosen HJ, Boxer AL, Elahi FM, Kornak J, Mungas D, Kramer JH. Development and validation of the Uniform Data Set (v3.0) executive function composite score (UDS3-EF). Alzheimers Dement. 2021 Apr;17(4):574-583. doi: 10.1002/alz.12214. Epub 2020 Nov 20.