Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia Consortium

Dementia Clinical Trial

— MarkVCID  

Official title:

Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia Consortium

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06284213
• Other study ID #: 5U24NS100591
• Status: Recruiting
• Start date: September 29, 2021
• Est. completion date: July 2027

Study information

• Verified date: February 2024
• Source: Massachusetts General Hospital
• Contact: Herpreet Singh, MA
• Phone: 617-643-3871
• Email: HSINGH6[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1800
• Est. completion date: July 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Cognitive Impairment
• Dementia

Intervention

Other:
• No interventions
This is an observational study with no interventions.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	Rush University Medical Center & Illinois Institute of Technology	Chicago	Illinois
United States	University of Texas Southwestern	Dallas	Texas
United States	University of Texas Health Science Center Houston	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	University of California Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of California Davis	Sacramento	California
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Texas Health Science Center San Antonio	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	Olive View - UCLA Medical Center	Sylmar	California

Sponsors (18)

Lead Sponsor

Collaborator

Massachusetts General Hospital

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

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SVD progression as measured by decline in global cognition	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	SVD progression as measured by decline in executive function	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.