Clinical trial NCT06856681: Clinical Utility of Early Vs. Late Blood Biomarker Testing for Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Alzheimers Disease
Keywords: Blood biomarkers
Mild Cognitive Impairment
Dementia
Alzheimers disease
Lead sponsor: C2N Diagnostics
Sponsor class: INDUSTRY
Collaborators: name: Alzheimer's Association
First posted: 2025-03-04
Enrollment: 800
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study uses a parallel assignment interventional model in which participants are randomized into one of two groups to evaluate the impact of the timing of PrecivityAD2 test on physician diagnostic confidence and clinical decision-making. Participants in the early testing group receive their PrecivityAD2 test at Visit 1, while those in the delayed testing group receive their results at Visit 3 (Day 90). Both groups proceed independently through the study, and assessments occur at standardized time points to measure changes in diagnostic confidence, treatment decision, and diagnostic test utilization.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to achieve >=90% Diagnostic Confidence for AD or Non-AD
timeFrame: From enrollment until diagnosis, with primary assessment at Visit 2 (Day 90) and Visit 3 (Day 180).
measure: Proportion of Patients with AD of Non-AD Diagnosis
timeFrame: Assessed at Visit 2 (Day 90) and Visit 3 (Day 180)
Secondary outcomes:
measure: Time to Initiation or Modification of AD or Non-AD Therapy
timeFrame: Measured from enrollment through Visit 4 (Day 365).
measure: Proportion of patients on AD or non-AD prescription
timeFrame: Assessed at Visit 3 (150-210)
measure: Number and Type of Diagnostic Tests Ordered
timeFrame: Evaluated cumulatively at Visit 2 (Day 90), Visit 3 (Day 180), and Visit 4 (Day 365)
measure: Change in Physician Diagnostic Confidence
timeFrame: Collected at Enrollment/Baseline (Day 0), Visit 2 (Day 90), Visit 3 (Day 180) and Visit 4 (Day 365)
Other outcomes:
measure: Patient-Reported Experience with Diagnostic Process
timeFrame: Collected at Visit 2 (Day 90), Visit 3 (Day 180) and Visit 4 (Day 365)
measure: Caregiver-Reported Perception of Disease Burden
timeFrame: Collected at Visit 2 (Day 90), Visit 3 (Day 180) and Visit 4 (Day 365)
measure: Healthcare Utilization and Costs
timeFrame: Enrollment through Visit 4 (Day 365)
Locations:
Study officials:
affiliation: C2N Diagnostics
name: Vice President, Neurology
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.