Determining the Association of Microvascular Disease as Assessed by PET and Graft Injury by Donor Derived Cell Free DNA

NCT05756088 | Withdrawn

• 2 other identifiers: 2000034497YSI-004
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to understand if a blood test in people who have had heart transplants can detect and predict the following:

• Blockages in the small blood vessels of the heart.
• Whether small blockages can turn into more severe blockages in the future. Participants will undergo blood draws once every 3 months in the first year of the study (4 blood draws total, taking 15 minutes each) and their medical records will be reviewed for 3 years after the date they are enrolled in the study.

Conditions

Cardiac Allograft Vasculopathy; Endothelial Dysfunction; Microvascular Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• dd-cf DNA and myocardial flow reserve (MFR) on positron emission tomography (PET) scan.

  Changes in dd-cf DNA levels in subjects with low MFR compared to normal MFR.

  Baseline up to 1 year

Secondary Outcomes (7)

• Impact of low MFR on rejection

  3 years

• Impact of low MFR on left ventricular ejection fraction

  Baseline up to 3 years

• Impact of low MFR on need for revascularization

  3 years

• Impact of low MFR on myocardial infarction (MI)

  3 years

• Impact of low MFR on admissions for heart failure

  3 years

Study Arms (2)

Low MFR (less than or equal to 1.5)

Subjects who are found to have a low MFR of less than or equal to 1.5.

Diagnostic Test: Blood draw to measure the levels of dd-cf DNA

Normal MFR (greater than 1.5)

Subjects who are found to have normal MFR of greater than 1.5.

Diagnostic Test: Blood draw to measure the levels of dd-cf DNA

Interventions

Blood draw to measure the levels of dd-cf DNA DIAGNOSTIC_TEST

Blood draw to measure the levels of dd-cf DNA.

Low MFR (less than or equal to 1.5); Normal MFR (greater than 1.5)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

An anticipated total of 88 adults who are undergoing routine stress PET scans as part of post-transplant surveillance will be included. Patients who are at least 3 years from heart transplantation and who meet all eligibility criteria will be enrolled.

You may qualify if:

• The patient is over 18 years of age.
• The patient underwent orthotopic heart transplantation and is undergoing routine cardiac allograft vasculopathy (CAV) surveillance with PET.
• The patient has no evidence of cardiogenic shock.
• The patient has no evidence of acute rejection.
• The patient, or legally authorized representative, has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent, approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).
• Potential subjects will be excluded if any of the following conditions apply:

You may not qualify if:

• Evidence of moderate to large area of ischemia on the PET.
• Multiorgan transplantation.
• Life expectancy \<1 year due to non-cardiac conditions.
• Less than 3 years from transplantation.
• Patient appears unlikely or unable to participate in the required study procedures, as assessed by the study PI, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease).

Sponsors & Collaborators

• Yale University: lead
• Yale Cardiovascular Research Group: collaborator
• Natera, Inc.: collaborator

Study Sites (1)

Yale New Haven Health

New Haven, Connecticut, 06519, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

Study Officials

• Lavanya Bellumkonda, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: March 6, 2023
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (1)