Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia Consortium (MarkVCID)

February 27, 2024 updated by: Steven M. Greenberg, MD,PhD, Massachusetts General Hospital

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

1800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California Los Angeles
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • University of Southern California
        • Contact:
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California Davis
        • Contact:
      • San Francisco, California, United States, 94158
        • Recruiting
        • University of California San Francisco
        • Contact:
      • Sylmar, California, United States, 91342
        • Recruiting
        • Olive View - UCLA Medical Center
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center & Illinois Institute of Technology
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University
        • Contact:
          • Hanzhang Lu, PhD
          • Phone Number: 410-955-1431
          • Email: hlu3@jhmi.edu
      • Baltimore, Maryland, United States, 21201
    • Minnesota
      • Rochester, Minnesota, United States, 55901
        • Recruiting
        • Mayo Clinic Rochester
        • Contact:
          • Ronald Petersen, MD, PhD
          • Phone Number: 507-284-1588
          • Email: peter8@mayo.edu
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Recruiting
        • University of Mississippi Medical Center
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University in St. Louis
        • Contact:
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Recruiting
        • University of New Mexico
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas Health Science Center Houston
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Texas Health Science Center San Antonio
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Normal Cognition (NC) with at least 1 vascular risk factor

NC is defined as:

  1. No diagnosis of SCD, MCI, or dementia; AND
  2. CDR: Sum of Boxes = 0 AND neuropsychological testing in normal range.

Participants must have at least 1 of the following criteria prior to enrollment:

Diabetes (at least 1):

  • Fasting (8-hour) blood sugar ≥126 mg/dL
  • Random or Post-prandial blood sugar ≥200 mg/dL
  • HbA1C ≥6.5%
  • Treatment with anti-diabetic medicine

Hypertension plus (at least 2):

  • Use of anti-hypertensive medications for lowering blood pressure for ≥10 years
  • Current use of 2 or more anti-hypertensive meds for lowering blood pressure
  • Blood pressure in a research or clinical setting in the last 2 years with SBP ≥140 or DBP ≥90
  • Second blood pressure reading in a research or clinical setting in the last 2 years (different date) with SBP ≥140 or DBP ≥90
  • Evidence of likely HTN end organ damage

MRI factors (at least 1):

  • Peri-Ventricular Fazekas Extent Grade or Deep Fazekas Extent Grade ≥2
  • ≥1 microbleeds
  • ≥1 lacunar infarcts
Other: No interventions
This is an observational study with no interventions.
Subjective Cognitive Decline (SCD)

Subjective cognitive decline is defined as:

  1. Cognitive concerns based on a Short eCog-12 score ≥ 3 (based on administration to participant), AND
  2. Normal cognition (neuropsychological testing within normal range).
Other: No interventions
This is an observational study with no interventions.
Mild Cognitive Impairment (MCI)

Mild cognitive impairment is defined as:

  1. There is a cognitive concern, i.e., the subject, the co-participant, or a clinician is concerned about a change in cognition compared to the subject's previous level.
  2. There is impairment in one or more cognitive domains (memory, language, executive function, attention, and visuospatial skills) that is greater than would be expected for the patient's age and educational background.
  3. There is largely preserved independence in functional abilities (no change from prior level of functioning or requires only extra effort and minimal aids or assistance).
  4. There is no evidence of dementia (cognitive changes are mild and there is no evidence of a significant impairment in social or occupational functioning).
Other: No interventions
This is an observational study with no interventions.
Mild Dementia

Mild dementia is defined as:

  1. The subject has cognitive or behavioral (neuropsychiatric) symptoms that meet all of the following criteria:

    1. Interfere with ability to function as before at work or at usual activities?
    2. Represent a decline from previous levels of functioning?
    3. Are not explained by delirium or major psychiatric disorder? AND

  2. Impairment in one* or more of the following domains.

    1. Impaired ability to acquire and remember new information.
    2. Impaired reasoning and handling of complex tasks, poor judgment.
    3. Impaired visuospatial abilities.
    4. Impaired language functions.
    5. Changes in personality, behavior, or comportment * In the event of single-domain impairment (e.g., language in PPA, behavior in bvFTD, posterior cortical atrophy), the subject must not fulfill criteria for MCI.

    AND

  3. CDR: Global Score = 0.5 or 1
Other: No interventions
This is an observational study with no interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SVD progression as measured by decline in global cognition
Time Frame: The cognitive battery is implemented, and global cognition calculated, at Baseline and Years 1, 2 and 3 post-baseline.
Global cognition scores will be calculated at each study timepoint as an average of age- and education-specific z-scores, based on tests scores from the MarkVCID2 cognitive battery (MoCA, Neuropsychological Testing Battery, Clinical Dementia Rating), which is based on Version 3 of the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS) (Besser 2018).
The cognitive battery is implemented, and global cognition calculated, at Baseline and Years 1, 2 and 3 post-baseline.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SVD progression as measured by decline in executive function
Time Frame: The cognitive battery is implemented, and executive function calculated, at Baseline and Years 1, 2 and 3 post-baseline.
The measure of executive function is the Uniform Data Set (v3.0) executive function composite score (UDS3-EF) developed by Staffaroni et al (2021). The UDS3-EF is calculated from the following tests: Category Fluency - Animals; Verbal Fluency - Phonemic Tests (words beginning with F); Number Span Test (Backward); and Trail Making Tests A and B.
The cognitive battery is implemented, and executive function calculated, at Baseline and Years 1, 2 and 3 post-baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Johns Hopkins University
Mayo Clinic
The University of Texas Health Science Center, Houston
Washington University School of Medicine
University of Maryland, Baltimore
University of California, Los Angeles
Duke University
Rush University Medical Center
University of Southern California
University of California, Davis
University of California, San Francisco
University of Texas
The University of Texas Health Science Center at San Antonio
University of Kentucky
University of New Mexico
University of Mississippi Medical Center
Olive View-UCLA Education & Research Institute

Investigators

  • Principal Investigator: Steven M. Greenberg, MD, PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 29, 2021

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

February 16, 2024

First Submitted That Met QC Criteria

February 27, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 27, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5U24NS100591 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

MarkVCID research openly shares both within and outside the MarkVCID Consortium to the greatest extent practical. As per the MarkVCID Consortium's Charter, MarkVCID investigators are granted broad access to MarkVCID data, samples, analytic tools, and other resources with relevant permissions in place. MarkVCID data and samples may also be shared with external collaborators in compliance with the Consortium's external data sharing policies outlined in the MarkVCID Data Use Agreement. The process for requesting data and biosamples is described below.

IPD Sharing Time Frame

Internal

All MarkVCID research sites sign a Consortium Research Agreement governing the sharing of data and biosamples. Data entered in MarkVCID data systems by the research sites becomes available to all MarkVCID members, in accordance with the MarkVCID Data Sharing, Analysis, and Publications Policy and the MarkVCID Research Agreement.

External

If the request is approved by the MarkVCID Steering Committee, external users sign the DUA to gain access to the data. If biosamples are requested, external users will execute a Material Transfer Agreement (MTA) with the institution(s) providing samples. Biosamples typically ship within 3 months. Electronic data stored by the MarkVCID Consortium repository becomes available to the investigator about 3 weeks after project approval and signing of the DUA. Investigators requesting access to data and biosamples not held by the MarkVCID repository must contact relevant institution(s) and are subject to longer wait times.

IPD Sharing Access Criteria

A MarkVCID Project Proposal Form must be submitted for data and biosample requests. The form requires an overview, a description of requested data and/or biosamples, assays, experiments to be conducted, and publication plans. Data requests will be reviewed by the Sharing Subcommittee and biosample requests by the Fluid-Based Biomarkers Subcommittee. Reviews will be based on scientific rationale, overlap with already approved analyses, and, for biosample requests, the scientific priority of the study relative to the number of available biosamples. The Steering Committee will then review proposal recommendations and determine approval. Investigators with approved proposals will sign a DUA and receive applicable data via Globus encrypted transfer. Investigators with approved biosample requests will execute necessary MTAs and receive deidentified biosamples from holding sites.

Internal requests related to primary hypotheses of prespecified biomarker kits are exempt from the above.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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