Evaluation of Self-Mediated Alternatives for Risk Testing Education and Return of Results (eSMARTER)

This randomized non-inferiority study will evaluate self-directed scalable electronic health platform (eHealth) methods for communicating Alzheimer's gene and biomarker results compared to videoconference telehealth disclosure with healthcare providers, as well as characterize the impacts of learning this information on the participant.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Other: eHealth Platform; Other: Videoconference Telehealth Platform

Detailed Description

This is a randomized trial to evaluate self-directed scalable eHealth methods for communicating Alzheimer's gene and biomarker results, as well as characterize the clinical impacts of learning this information on the participant. All participants in the study will be randomized to receive their Alzheimer's gene and biomarker results either via person-mediated telehealth videoconference visit with a healthcare provider or by eHealth platform. A permuted block design will be used for randomization, and we will stratify by sex and apolipoprotein E (APOE) genotype.

Participants randomized to the eHealth arm will be offered either the ADWebPortal or ADChatbot but can switch between platforms or schedule a virtual appointment to speak with a healthcare provider at any point. Use of the pre-disclosure education platforms will be tracked. A HIPAA compliant telehealth application will be used for the person-mediated telehealth videoconference visits and sessions will be recorded.

Potential participants will be identified from the GeneMatch program. Study management and participation will be decentralized. Confirmation of eligibility and consent of potential participants will be completed remotely by a decentralized study team. Procedures requiring physical attendance (e.g., blood draw) will be completed remotely using mobile health services.

• Study Type: Interventional
• Enrollment (Actual): 681
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Accellacare Clinical Research Site 02
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Accellacare Clinical Research Site 01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Access to the internet and an internet-enabled device.
• Participant is able to provide informed consent as shown by correctly answering questions administered by the study coordinator during the electronic consenting process that assess understanding of consent form content.
• Participant is willing and has the ability to fully comply with study procedures defined in this protocol.
• Written and spoken fluency in the English.
• Participant agrees to undergo a blood draw for collection of a blood sample for future testing and repository storage.

Exclusion Criteria:

• Participant reports prior knowledge of APOE genotype.

• Lack of psychological readiness to receive AD gene and biomarker information as indicated by:

  1. obtaining a score of 10 or greater on the Patient Health Questionnaire - 9 (PHQ-9) AND/OR
  2. responding yes on any of the suicidal ideation questions extracted from the abbreviated Columbia Suicide Severity Scale (C-SSRS) or AD Specific Suicidality Questions.
• Presence of current major psychiatric illness, e.g., psychosis, bipolar disorder, PTSD

• Communication difficulties such as:

  1. Uncorrected or uncompensated hearing and/or vision impairment.
  2. Uncorrected or uncompensated speech defects.

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: eHealth platform; The eHealth platform consists of the self-directed web-portal (ADWebPortal) and chatbot (ADChatbot) to receive their Alzheimer's-related test results. Participants randomized to this arm can switch between the two or schedule a virtual appointment with a healthcare provider.	Other: eHealth Platform; The eHealth Platform consists of the ADWebPortal and ADChatbot for receiving Alzheimer's-related test results
Active Comparator: Videoconference telehealth; The videoconference telehealth platform consists of remote visit(s) with a healthcare provider to receive their Alzheimer's-related test results.	Other: Videoconference Telehealth Platform; Participants will have a video telehealth visit with a healthcare provider to receive Alzheimer's-related test results

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety as measured by the PROMIS Anxiety scale	Anxiety scale	T2 minus T1 change scores (6-weeks post disclosure minus 0-7 days post disclosure)
Knowledge of Genetic Disease as measured by an 8-item scale adapted from the Cancer Genetics Knowledge Scale and ClinSeq Knowledge Scale	Knowledge of Genetic Disease scale	T2 minus T1 change scores (6-weeks post disclosure minus 0-7 days post disclosure)
Disease-specific distress as measured by an 8-item scale adapted from the Impact of Events Scale	Disease-specific distress scale	T2 minus T1 change scores (6-weeks post disclosure minus 0-7 days post disclosure)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression as measured by the Patient Health Questionnaire - 9 (PHQ-9)	Depression scale	0-7 days, 6 weeks, 6 months
Psychological wellbeing as measured by a 14-item scale adapted from the Psychological Wellbeing Scale	Psychological wellbeing scale	6 months
Perceived risk of Alzheimer's as measured by a scale adapted from the REVEAL Study	Perceived risk of Alzheimer's scale	0-7 days, 6 weeks, 6 months
Impact of disclosure as measured by the 16-item IGT-AD scale	Impact of genetic testing for Alzheimer's disease (IGT-AD) scale	0-7 days, 6 weeks, 6 months
Subjective cognitive concerns as measured by the 14-item Cognitive Function Instrument	Subjective cognitive concerns scale	6 months
Stigma as measured by the 6-item Stigma Impact Scale	Stigma scale	0-7 days, 6 weeks, 6 months

Collaborators and Investigators

• Sponsor: Banner Health
• Collaborators: University of Pennsylvania; National Institute on Aging (NIA)
• Investigators: Principal Investigator: Jessica Langbaum, PhD, Banner Alzheimer's Institute

Publications and helpful links

General Publications

• Erickson CM, Langlois CM, Wood EM, Mim R, Howe S, Ofidis D, Egleston BL, Harkins K, Largent EA, Roberts JS, Reiman EM, Denkinger M, Ashton NJ, Karlawish J, Bradbury AR, Langbaum JB. Evaluation of self-mediated alternatives for risk testing education and return of results (eSMARTER) study: A randomized study of methods for returning APOE and pTau-217 results. Alzheimers Dement (N Y). 2025 Nov 16;11(4):e70177. doi: 10.1002/trc2.70177. eCollection 2025 Oct-Dec.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Actual): November 7, 2025
• Study Completion (Actual): November 7, 2025

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 14, 2024

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: APOE
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: API-0001; R01AG058468 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Trial dataset and biological samples will be shared with qualified investigators
• IPD Sharing Time Frame: Data will be shared within 12 months after study completion
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No