NCT02752789

Brief Summary

This is a multi-center, prospective, single cohort, observational study of pediatric heart transplant recipients designed to determine the impact of preformed versus de novo human leukocyte antigen (HLA) donor-specific antibodies (DSA), and antibodies to the self-antigens cardiac myosin and vimentin, on chronic allograft function. In addition, the investigators will explore mechanisms of action and predictors of DSA, rejection and altered pathophysiology.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
407

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jul 2014

Longer than P75 for all trials

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 15, 2014

Completed
1.8 years until next milestone

First Submitted

Initial submission to the registry

April 22, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 27, 2016

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2019

Completed
Last Updated

November 29, 2019

Status Verified

November 1, 2019

Enrollment Period

5.3 years

First QC Date

April 22, 2016

Last Update Submit

November 27, 2019

Conditions

Keywords

alloantibodiesdonor specific antibodies (DSA)-preformed, de novoself-antigenschronic allograft function

Outcome Measures

Primary Outcomes (1)

  • Pulmonary capillary wedge pressure at heart catheterization

    3 years post-transplantation

Secondary Outcomes (16)

  • Other invasive cardiac hemodynamic findings at cardiac catheterization

    3 and 5 years post-transplantation

  • Frequency of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin

    3 years post-transplantation

  • Time course of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin.

    3 years post-transplantation

  • Frequency of first episode of late acute rejection

    From >1 year to 5 years post-transplantation

  • Time to first episode of late acute rejection

    From >1 year to 5 years post-transplantation

  • +11 more secondary outcomes

Other Outcomes (4)

  • Exploratory: Microvascular pathology

    Up to 5 years post-transplantation

  • Exploratory: Expression of cytoprotective genes Bcl2 and HO-1, ICAM, VCAM and selectins, Complement inhibitory proteins CD55, CD59, CR1, CR2 and CR3.

    After exposure to alloantibody (or control) (At Year 1)

  • Exploratory: Cellular immune responses to allo-antigens and self-antigens (vimentin and myosin)

    24 hours prior transplantation, Months 3 and 6 post transplantation

  • +1 more other outcomes

Study Arms (1)

Pediatric Heart Transplant Recipients

CTOTC-04 (ClinicalTrials.gov ID NCT01005316) participants who consent to long-term follow-up as part of this study as well as candidates less than 21 years of age who are listed for isolated orthotopic heart transplantation at one of the participating sites

Eligibility Criteria

AgeUp to 20 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Participants that were enrolled in CTOTC-04 (ClinicalTrials.gov ID NCT01005316) who consent to long-term follow-up and new participants at the nine designated sites who are listed for isolated orthotopic heart transplantation

You may qualify if:

  • Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
  • Planned long-term follow-up at one of the study sites
  • AND either:
  • Enrolled in the CTOTC-04 study and actively followed at one of the study sites
  • Listed at participating study sites, less than 21 years of age and not yet transplanted.

You may not qualify if:

  • Parental withdrawal of consent from the CTOTC-04 study
  • Past or current medical problems or findings from physical examination or laboratory testing that, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
  • Listed for simultaneous multiple organ transplant.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Emory University School of Medicine

Atlanta, Georgia, 30060, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Children's Hospital at Montefiore

New York, New York, 10467, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Monroe Carell Jr. Children's Hospital

Nashville, Tennessee, 37232, United States

Location

Hospital for Sick Children

Toronto, M5G 1X8, Canada

Location

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, PBMC and tissue

Study Officials

  • Steven A. Webber, MBChB, MRCP

    Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric Transplantation

    STUDY CHAIR
  • Steven A. Webber, MBChB, MRCP

    Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric Transplantation

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 22, 2016

First Posted

April 27, 2016

Study Start

July 15, 2014

Primary Completion

November 1, 2019

Study Completion

November 1, 2019

Last Updated

November 29, 2019

Record last verified: 2019-11

Locations