Clinical Trial of the Sequence of Cardiovascular Genetic Counseling and Testing (RESEQUENCEGC)

Randomized Clinical Trial of the Sequence of Genetic Counseling and Testing to Optimize Efficiency, Patient Empowerment and Engagement, and Medical Adherence for Diverse Genetic Testing Indications

Although pre-test genetic counseling is widely recommended and has come to dominate genetic counseling practice, tailored results-focused genetic counseling could both increase genetic counseling efficiency and improve genetic counseling outcomes for the growing number of patients seeking genetic testing for recommended genome-guided medical management. This study will test that hypothesis in adults referred for cardiovascular genetic counseling and testing at the Johns Hopkins Center for Inherited Heart Diseases. This study is a three-arm randomized clinical trial to evaluate two complementary approaches to shifting the primary genetic counseling session to post-test for 510 adults with two broad cardiovascular genetic counseling indications: diagnostic panel testing and family-specific variant testing. The investigators will compare usual care (pre-test genetic counseling appointment, results returned by phone / electronic health record) with online video-based pre-test tailored genetic education with an optional (efficiency arm) or required (flipped arm) phone call with a genetic counselor followed by a post-test genetic counseling appointment. The investigators hypothesize that post-test genetic counseling will: 1) increase efficiency, 2) promote patient empowerment and adherence, and 3) have similar genetic test-associated psychosocial impact.

Study Overview

• Status: Active, not recruiting
• Conditions: Genetic Counseling; Inherited Cardiac Disease
• Intervention / Treatment: Behavioral: post-test cardiovascular genetic counseling with pre-test education by video; Behavioral: optional phone call with genetic counselor pre-test; Behavioral: required phone call with genetic counselor pre-test

Detailed Description

This is a three-arm randomized clinical trial with a parallel-group design comparing usual care (pre-test genetic counseling, test results by phone/electronic health record (EHR)) to two approaches to post-test results-focused genetic counseling involving a pre-test educational video with an optional [efficiency arm] or required [flipped arm] phone call with a genetic counselor followed by a post-test genetic counseling appointment. Consented participants will be randomly allocated to the three study arms stratified by genetic testing indication (cardiovascular panel, family-specific variant). Questionnaires will be administered at 4 timepoints: 2 weeks before pre-test education/counseling (Q1), immediately after pre-test education/counseling and test ordered or declined (Q2), 2-weeks post-disclosure (Q3), and 6-months post-disclosure (Q4) (Aims 1-3). Data will be extracted from each participant's electronic health record (EHR) to record potential clinical covariates (Aims 1-3), validate self-reported adherence to medical recommendations (Aim 3), and obtain metrics to measure genetic counseling efficiency (Aim 4).

• Study Type: Interventional
• Enrollment (Actual): 393
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Cardiovascular panel testing inclusion criteria:

1. Adult (age 18+) scheduled for outpatient genetic counseling in the Johns Hopkins Center for Inherited Heart Diseases,
2. Clinical diagnosis or suspected clinical diagnosis of a potentially inherited cardiovascular disease including a) hypertrophic, dilated, or arrhythmogenic cardiomyopathy, b) ventricular or atrial arrhythmias or an ECG-pattern suspicious for an inherited cardiovascular disease including catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, or Brugada syndrome, or c) a diagnosed or suspected lipid disorder or early-onset coronary artery disease,
3. next-generation cardiovascular sequencing panel clinically indicated.

Family specific variant testing inclusion criteria:

1. Adult (age 18+) scheduled for outpatient genetic counseling in the Johns Hopkins Center for Inherited Heart Diseases,
2. Documented pathogenic or likely pathogenic variant in a gene associated with a hereditary cardiomyopathy, arrhythmia syndrome, or lipid disease in a family member,
3. Referred to the Center for Inherited Heart Diseases for family-specific variant testing.

Exclusion Criteria:

1. Previous genetic counseling at Johns Hopkins for this clinical indication,
2. Previous genetic testing that definitively identified the genetic cause of the patient's condition,
3. Patient unable to speak or read English,
4. Genetic counseling appointment is not anticipated to include genetic testing (for instance if it was scheduled to discuss family communication or adaptation to a new diagnosis),
5. Next generation sequencing panel not clinically indicated (panel cohort only).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care; Pre-test genetic counseling appointment with results returned by phone or EHR. Post-test appointment available upon request.
Experimental: Efficiency; Pre-test genetics education by educational video with an OPTIONAL call with a genetic counselor to address questions. Pre-test appointment available by request. Post-test genetic counseling appointment.	Behavioral: post-test cardiovascular genetic counseling with pre-test education by video; post-test cardiovascular genetic counseling with pre-test education by video; Behavioral: optional phone call with genetic counselor pre-test; OPTIONAL phone call with genetic counselor pre-test
Experimental: Flipped; Pre-test genetics education by educational video with a REQUIRED call with a genetic counselor to address questions. Pre-test appointment available by request. Post-test genetic counseling appointment.	Behavioral: post-test cardiovascular genetic counseling with pre-test education by video; post-test cardiovascular genetic counseling with pre-test education by video; Behavioral: required phone call with genetic counselor pre-test; REQUIRED phone call with genetic counselor pre-test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in empowerment as measured on the Genetic Counseling Outcomes Scale (GCOS)	Change in empowerment as measured on the Genetic Counseling Outcomes Scale (GCOS). The GCOS is 24-item Likert scale with a 7-item response set. Scores range from 24-168 with higher scores indicating higher empowerment.	Baseline up to 2-weeks after genetic counseling result appointment / disclosure
Anxiety as measured on the Hospital Anxiety and Depression Scale (HADS)	Anxiety as measured on the Hospital Anxiety and Depression Scale (HADS). The HADS contains 14 items measured on a 4-point Likert scale. The anxiety subscale contains 7 items. HADS subscale scores ≥8 indicate potentially clinically significant anxiety and depression and scores ≥10 a likely case.	6-months post results disclosure
Medical adherence as assessed by proportion of completed screening tests	Proportion of recommended cardiology appointments and screening tests completed or scheduled	6-months post results disclosure
Efficiency as assessed by minutes of direct counseling time	Total minutes of counseling time per patient documented in the electronic health record including visit and phone notes.	Up to 6-months post results disclosure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in engagement as assessed by Patient Activation Measure	Change in patient engagement as measured by the short form of the Patient Activation Measure (PAM-13). The PAM-13 includes a 4-item Likert scale response set with higher scores indicating higher patient activation. To calculate the total PAM score, the raw score is divided by the number of items answered (excepting non-applicable items) and multiplied by 13. Then, this score is transformed to a scale with a theoretical range 0-100, based on calibration tables, with higher PAM scores indicating higher patient activation.	Baseline, 6-months post results disclosure
Informed Choice as assessed by Multidimensional Model of informed Choice pilot scales	Multidimensional Model of informed Choice pilot scales for familial hypercholesterolemia (FH) and cardiomyopathy/arrhythmia testing will be used. This is a scale that combines a subscale with 8 True/false knowledge about cardiovascular genetics and genetic testing questions scored as number correct with a 5-item scale with a Likert scale response set assessing attitudes toward genetic testing. The entire scale is scored by combining knowledge, values and testing choice made.	up to 14 days post-education

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Human Genome Research Institute (NHGRI)
• Investigators: Principal Investigator: Cynthia James, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Actual): May 21, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: inherited heart disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases
• Other Study ID Numbers: IRB00320656; R01HG011902 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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