Clinical trial NCT04656080: Cardiopulmonary Stress Testing (CPET) AlloSure Study
Official title: 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?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Heart Failure
Transplant; Failure, Heart
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2020-12-07
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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?

Eligibility criteria: 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.

Primary outcomes:
measure: • Cell-free DNA (AlloSure) levels after maximal cardiopulmonary exercise
timeFrame: 10 days
measure: • Comparison of maximal oxygen consumption (VO2)
timeFrame: 10 days
measure: • Comparison of level of cell-free DNA
timeFrame: 10 days
Secondary outcomes:
measure: • Time-dependent changes in high-sensitivity troponin-levels
timeFrame: 10 days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor Scott & White health research institute
state: Texas
Study officials:
affiliation: BSWRI
name: Robert Gottlieb, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.