Clinical Utility of Early vs. Late Blood Biomarker Testing for Alzheimer's Disease (ADELAIDE)

A Study of the Clinical Effect of the Implementation of a Blood Biomarker Into Memory Clinics in the Department of Veterans Affairs and Other Closed System Healthcare Memory and Dementia Sites in the United States

The goal of this study is to evaluate whether use of the PrecivityAD2 blood biomarker assay with early result disclosure along with discretionary Precivity-ApoE proteotype testing will shorten the time to Alzheimer's Disease or non-Alzheimer's diagnosis as compared to delayed result disclosure.

Participants will be randomized into the early PrecivityAD2 blood biomarker test & disclosure group (Cohort A) or to the later PrecivityAD2 blood biomarker test & disclosure group (Cohort B) where blood samples will be collected and tested using the PrecivityAD2 test at Visit 1 (day 0) and Visit 2 (day 90). Participants will attend study visits for one year after their enrollment. An optional sub-study will be offered to collect information through questionnaires at each visit regarding participant's and their care-giver's experiences through the AD diagnostic journey.

Study Overview

• Status: Withdrawn
• Conditions: Alzheimers Disease
• Intervention / Treatment: Diagnostic test: PrecivityAD2 - Early Testing; Diagnostic test: PrecivityAD2 - Delayed Testing

Detailed Description

Healthcare providers engaged in memory care and Alzheimer's disease (AD) management have shown significant interest in the performance of plasma tests. A collaboration with Veteran's Affairs (VA) and other closed healthcare systems represents an opportunity to examine the clinical validity and utility of blood biomarkers (BBM). The ADELAIDE study is a prospective, randomized, clinical utility, economic impact and real-world study. The BBM test under study is the PrecivityAD2 blood test that uses high-resolution liquid chromatography mass spectrometry to measure plasma Aβ42/40 and p-tau217/np-tau217 ratios. This study will assess and quantify the impact of BBM testing to overall time-to-diagnosis and time to prescription of an appropriate Alzheimer's Disease (AD) or non-AD therapy. Additionally, this study will assess the impact of BBM testing to procedure utilization and overall costs of healthcare and will assess the diagnostic confidence of clinicians that order the test.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Minimum age: 50 years.
2. Patients presenting with symptoms of mild cognitive impairment (MCI) or other cognitive impairments in which the enrolling clinician clinically suspects Alzheimer's pathology as the primary cause of symptomatic presentation
3. Patients presenting with mixed brain pathologies including MCI/ cognitive impairments in which the investigator clinically suspects Alzheimer's pathology as the primary or contributing cause of symptomatic presentation
4. Patients are able to attend study visits and standard care visits over the period of 1 year from the date of enrollment
5. Patients are able to undergo routine phlebotomy and provide up to six (6) 10 ml tube(s) of blood for study related tests plus any additional blood necessary for standard laboratory testing at each study timepoint
6. Patients are able to undergo standard care diagnostic procedures to include MRI (or CT), amyloid PET and/or CSF biomarker testing for AD diagnosis if prescribed by investigator
7. Patients are able to provide informed consent. Or, if in the opinion of the clinician, the patient is unable to adequately understand the nature of the trial and protocol requirements, a family member or appropriate representative of the patient is present to consent, with additional assent by the patient.

Exclusion Criteria

1. Patients younger than 50 years of age
2. Patients being evaluated for cognitive impairment known to be predominantly the result of a disease or condition other than AD
3. Patients previously diagnosed with AD, unless the ADELAIDE investigator has a strong clinical suspicion suggestive of an incorrect initial diagnosis upon referral
4. Patients with no cognitive impairment or clinical symptoms of AD
5. Patients desiring genetic testing for Alzheimer's disease markers without current cognitive impairment or other relevant clinical symptoms
6. Patients who are not able or not willing to undergo standard care diagnostic procedures to include MRI (or CT), amyloid PET and/or CSF biomarker testing for AD diagnosis as prescribed by investigator
7. Patients who are not able to understand the nature of the study nor the study requirements and not represented by a family member or other appropriate representative who is able to consent on behalf of the patient
8. Patients who are not able to commit to attending the required study and/or standard care visits
9. Patients who are not able to undergo routine phlebotomy or provide blood samples in the quantity required by the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Testing Group (Cohort A); Participants in this group will have blood drawn from the PrecivityAD2 test at Visit 1 (Day 0). Physicians will use these results in clinical decision-making from that point forward.	Diagnostic test: PrecivityAD2 - Early Testing; Participants in Cohort A will receive PrecivityAD2 testing at Visit 1, with results disclosed shortly after testing.
Experimental: Delayed Testing Group (Cohort B); Participants in this group will have blood drawn for the PrecivityAD2 test at Visit 2 (Day 90). Until then, standard clinical decision-making will process without access to PrecivityAD2 results.	Diagnostic test: PrecivityAD2 - Delayed Testing; Participants in Cohort B will receive PrecivityAD2 testing at Visit 2, with results disclosed shortly after testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to achieve >=90% Diagnostic Confidence for AD or Non-AD	Number of days from enrollment to achieving a diagnostic confidence score of >=90% for AD or non-AD diagnosis (based on physician survey).	From enrollment until diagnosis, with primary assessment at Visit 2 (Day 90) and Visit 3 (Day 180).
Proportion of Patients with AD of Non-AD Diagnosis	Proportion of patients with a confirmed AD or non-AD diagnosis with a diagnostic confidence score of >=90%.	Assessed at Visit 2 (Day 90) and Visit 3 (Day 180)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Initiation or Modification of AD or Non-AD Therapy	Number of days from enrollment to the prescription, initiation, or modification of an AD or non-AD therapy. Data will be sourced from medical records and recorded in eCRF.	Measured from enrollment through Visit 4 (Day 365).
Proportion of patients on AD or non-AD prescription	Proportion of patients on AD or non-AD prescription (e.g., DMT, treatments for DLB/PDD or VaD, cholinesterase inhibitors, other) at Visit 3 (150-210).	Assessed at Visit 3 (150-210)
Number and Type of Diagnostic Tests Ordered	Total number and type of additional diagnostic tests ordered (e.g., amyloid PET, MRI, CSF biomarkers) from Visit 2 (Day 90) through the date of AD or non-AD diagnosis with physician confidence >=90%. Data will be collected via physician-reported case forms.	Evaluated cumulatively at Visit 2 (Day 90), Visit 3 (Day 180), and Visit 4 (Day 365)
Change in Physician Diagnostic Confidence	Comparison of physician reported confidence of AD or non-AD diagnosis (0-100%) before and after receiving PrecivityAD2 results. Confidence scores will be collected by physician survey.	Collected at Enrollment/Baseline (Day 0), Visit 2 (Day 90), Visit 3 (Day 180) and Visit 4 (Day 365)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Reported Experience with Diagnostic Process	Patient-reported experience with the diagnostic journey, including perception of the clarity and utility of PrecivityAD2 results. Assessed using patient surveys.	Collected at Visit 2 (Day 90), Visit 3 (Day 180) and Visit 4 (Day 365)
Caregiver-Reported Perception of Disease Burden	Caregiver-reported assessment of disease burden, changes in the patient's condition, and perceived impact on daily life. Collected through structured caregiver surveys.	Collected at Visit 2 (Day 90), Visit 3 (Day 180) and Visit 4 (Day 365)
Healthcare Utilization and Costs	Total healthcare costs associated with diagnostic evaluations, physician visits, and treatments. Healthcare utilization and cost data will be collected from medical records and analyzed retrospectively after Visit 4 (Day 365).	Enrollment through Visit 4 (Day 365)

Collaborators and Investigators

• Sponsor: C2N Diagnostics
• Collaborators: Alzheimer's Association
• Investigators: Study Director: Vice President, Neurology, C2N Diagnostics

Publications and helpful links

General Publications

• Meyer MR, Kirmess KM, Eastwood S, Wente-Roth TL, Irvin F, Holubasch MS, Venkatesh V, Fogelman I, Monane M, Hanna L, Rabinovici GD, Siegel BA, Whitmer RA, Apgar C, Bateman RJ, Holtzman DM, Irizarry M, Verbel D, Sachdev P, Ito S, Contois J, Yarasheski KE, Braunstein JB, Verghese PB, West T. Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Abeta42/40 ratio to identify presence of brain amyloid. Alzheimers Dement. 2024 May;20(5):3179-3192. doi: 10.1002/alz.13764. Epub 2024 Mar 16.
• Palmqvist S, Tideman P, Mattsson-Carlgren N, Schindler SE, Smith R, Ossenkoppele R, Calling S, West T, Monane M, Verghese PB, Braunstein JB, Blennow K, Janelidze S, Stomrud E, Salvado G, Hansson O. Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care. JAMA. 2024 Oct 15;332(15):1245-1257. doi: 10.1001/jama.2024.13855.
• Schindler SE, Galasko D, Pereira AC, Rabinovici GD, Salloway S, Suarez-Calvet M, Khachaturian AS, Mielke MM, Udeh-Momoh C, Weiss J, Batrla R, Bozeat S, Dwyer JR, Holzapfel D, Jones DR, Murray JF, Partrick KA, Scholler E, Vradenburg G, Young D, Algeciras-Schimnich A, Aubrecht J, Braunstein JB, Hendrix J, Hu YH, Mattke S, Monane M, Reilly D, Somers E, Teunissen CE, Shobin E, Vanderstichele H, Weiner MW, Wilson D, Hansson O. Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease. Nat Rev Neurol. 2024 Jul;20(7):426-439. doi: 10.1038/s41582-024-00977-5. Epub 2024 Jun 12.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 26, 2025
• First Posted (Actual): March 4, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Mild Cognitive Impairment; Dementia; Blood biomarkers; Alzheimers disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Dementia
• Other Study ID Numbers: 250

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No