Cardiopulmonary Stress Testing (CPET) AlloSure Study

AlloSure Test Characteristics in Immunologically Quiescent and Immunologically Active Heart Transplant Recipients: Does Maximal Cardiopulmonary Stress Testing Prior to Assay Preserve Test Specificity While Enhancing Sensitivity?

1. Cell-free DNA does not vary significantly as a function of the activity of immunologically quiescent cardiac transplant recipients, despite the metabolic demands of the transplanted organ. (The implication of the null result would be that no restrictions to patient activity, nor modification of cardiac rehabilitation prescription, would be necessary to maintain proper test characteristics of AlloSure testing).
2. In immunologically active cardiac transplant allografts, exercise prior to assay of donor-derived cell-free DNA can be used to increase the sensitivity of the AlloSure test. (The implication of this would be that the optimal time-frame for drawing an Allosure may actually be post-exercise, and that window will be characterized).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Transplant; Failure, Heart
• Intervention / Treatment: Behavioral: CPET exercise testing

Detailed Description

The specific research questioned aimed to be addressed with this proposed study are:

i. Are dd-cfDNA levels in heart transplant recipients independent of recent cardiopulmonary exercise? More specifically, does the metabolic demand of maximal cardiopulmonary exercise in recent heart transplant recipients trigger a release of dd-cfDNA (if so, then what is the time course for resolution back to baseline?) ii. If dd-cfDNA does not release to any significant degree with cardiac allografts with short donor-ischemic time, does this test characteristic continue to hold for cardiac allografts transplanted after longer donor ischemic times? iii. In cardiac transplant recipients with medically stabilized, treated antibody-mediated rejection (AMR) and persistent dd-cfDNA elevation, does a discrete episode of maximal cardiometabolic activity trigger any additional elevation of dd-cfDNA, and again, with what time course?

• Study Type: Observational
• Enrollment (Estimated): 27

Contacts and Locations

• Study Contact: Name: Aayla Jamil, MBBS MPH; Phone Number: 214-820-1675; Email: Aayla.Jamil@BSWHealth.org

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor Scott & White Health research institute
      • Contact: Aayla Jamil, MBBS MPH; Phone Number: 214-820-1675; Email: Aayla.Jamil@BSWHealth.org

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The subjects to be enrolled in this study will be male and/or female hemodynamically stable outpatients who have undergone orthotopic heart transplant within three months from enrollment date for the recent transplant cohort, and within 10 years of transplant for the antibody-mediated rejection cohort. All subjects will be 18 to 80 years of age. All subjects must be able to read and understand an informed consent to be enrolled in the study.

For the stabilized antibody-mediated rejection cohort, only patients with invasive coronary angiography indicating no more than ISHLT grade 1 coronary allograft vasculopathy within 6 months prior to testing will be included.

Description

Inclusion Criteria:

Post-orthotopic heart transplant patients

Exclusion Criteria:

1. orthopedic, neurologic and/or any other limitations that do not allow for exercise testing on a treadmill or cycle ergometer;
2. individuals who require supplemental oxygen or have current permanent tracheostomies will be excluded from this study;
3. individuals who are discharged to a long-term acute care facility;
4. skilled nursing facility or with palliative care or hospice care will be excluded; (e) inmates and pregnant women;

(f) patients with antibody-mediate rejection that are not felt to be safe for cardiopulmonary stress testing.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
transplant recipients <1year without AMR; 20 recent transplant recipients (<1 year) without antibody-mediated rejection (AMR);	Behavioral: CPET exercise testing; The cardiopulmonary exercise testing (CPET) is done.; EKG testing will be done as part of the CPET test. Allosure testing will be done at baseline and then at 1 hr, 4 hrs, 1 day, 7 days after CPET.
3 months post-heart transplant with AMR; • 7 transplant recipients, at least 3 months post-transplant, with antibody-mediated rejection	Behavioral: CPET exercise testing; The cardiopulmonary exercise testing (CPET) is done.; EKG testing will be done as part of the CPET test. Allosure testing will be done at baseline and then at 1 hr, 4 hrs, 1 day, 7 days after CPET.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Cell-free DNA (AlloSure) levels after maximal cardiopulmonary exercise	• Cell-free DNA (AlloSure) levels after maximal cardiopulmonary exercise	10 days
• Comparison of maximal oxygen consumption (VO2)	• Comparison of maximal oxygen consumption (VO2)	10 days
• Comparison of level of cell-free DNA	Comparison of level of cell-free DNA	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Time-dependent changes in high-sensitivity troponin-levels	• Time-dependent changes in high-sensitivity troponin-levels	10 days

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Investigators: Principal Investigator: Robert Gottlieb, MD, BSWRI

Publications and helpful links

General Publications

• Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J. Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin. Cell. 2016 Jan 14;164(1-2):57-68. doi: 10.1016/j.cell.2015.11.050.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 6, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 020-188

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