NCT01985412

Brief Summary

The purpose of this study is to determine whether shotgun sequencing technology, which can be used to detect donor DNA in recipient plasma, can be used as a rapid, accurate, non-invasive method to detect Acute Cellular Rejection (ACR) after heart transplantation. Currently, all heart transplant recipients undergo invasive heart biopsies to diagnose ACR. Thus, there is an ongoing need to monitor patients for the development of acute and chronic rejection, with the primary goal of non-invasive early detection and treatment to prevent organ damage.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
65

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Mar 2010

Typical duration for all trials

Geographic Reach
1 country

2 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

March 1, 2010

Completed
3.2 years until next milestone

First Submitted

Initial submission to the registry

May 28, 2013

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 29, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 29, 2013

Completed
2 months until next milestone

First Posted

Study publicly available on registry

November 15, 2013

Completed
Last Updated

October 4, 2019

Status Verified

October 1, 2019

Enrollment Period

3.6 years

First QC Date

May 28, 2013

Last Update Submit

October 2, 2019

Conditions

Cardiac Transplant RejectionLung Transplant Rejection

Keywords

RejectionTransplantCardiacPulmonaryHeartLungCell-Free DNAcfDNACellFreeDNABiopsyNon-Invasive

Outcome Measures

Primary Outcomes (1)

  • Proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.

    We will use high throughput next generation sequencing to monitor the proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.

    The outcome measure is assessed for each patient up to 5 years post-transplant. Sampling timepoints include: Days 1, 2, 3, Weeks 1, 2, 4, 6, 8, 10, 12, Months 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and quarterly through year 5

Study Arms (5)

Adult Heart Transplant Recipients

Patients \>18 yrs old that received a heart-only transplant and are followed at Stanford Hospital

Pediatric Heart Transplant Recipients

Patients \<18 yrs old that received a heart-only transplant and are followed at Lucile Packard Hospital

Adult Lung Transplant Recipients

Patients \>18 yrs old that received a lung-only transplant and are followed at Stanford Hospital

Pediatric Lung Transplant Recipients

Patients \<18 yrs old that received a lung-only transplant and are followed at Lucile Packard Hospital

Kaiser Adult Heart Transplant Recipients

Patients \>18 yrs old that received a heart-only transplant at Stanford Hospital but are followed at Kaiser Permanente in Santa Clara

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Stanford and Lucille Packard adult and pediatric, lung or heart transplant recipients and Kaiser adult heart transplant recipients.

You may qualify if:

  • All ages of heart or lung transplant recipients
  • Recipients of re-do heart or re-do lung transplants

You may not qualify if:

  • Patients wait-listed for multiple organ transplantation (e.g. heart-kidney, heart-liver, heart and lung.)
  • Unable or unwilling to return to Stanford for biopsy and follow-up procedures
  • Followed by Palo Alto VA Hospital after transplant surgery (VA patients are transplanted at Stanford, but all subsequent clinical care is performed at VA hospitals)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Kaiser Permanente Northern California

Santa Clara, California, 95051, United States

Location

Stanford University Hospital and Clinics

Stanford, California, 94305, United States

Location

Related Publications (6)

  • Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34. doi: 10.1073/pnas.1013924108. Epub 2011 Mar 28.

    PMID: 21444804BACKGROUND

  • De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H, Neff NF, Okamoto J, Snyder TM, Cornfield DN, Nicolls MR, Weill D, Bernstein D, Valantine HA, Quake SR. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell. 2013 Nov 21;155(5):1178-87. doi: 10.1016/j.cell.2013.10.034.

    PMID: 24267896RESULT

  • De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.

    PMID: 24944192RESULT

  • Keller M, Bush E, Diamond JM, Shah P, Matthew J, Brown AW, Sun J, Timofte I, Kong H, Tunc I, Luikart H, Iacono A, Nathan SD, Khush KK, Orens J, Jang M, Agbor-Enoh S. Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD). J Heart Lung Transplant. 2021 Jun;40(6):488-493. doi: 10.1016/j.healun.2021.02.008. Epub 2021 Feb 20.

    PMID: 33814284DERIVED

  • Agbor-Enoh S, Jackson AM, Tunc I, Berry GJ, Cochrane A, Grimm D, Davis A, Shah P, Brown AW, Wang Y, Timofte I, Shah P, Gorham S, Wylie J, Goodwin N, Jang MK, Marishta A, Bhatti K, Fideli U, Yang Y, Luikart H, Cao Z, Pirooznia M, Zhu J, Marboe C, Iacono A, Nathan SD, Orens J, Valantine HA, Khush K. Late manifestation of alloantibody-associated injury and clinical pulmonary antibody-mediated rejection: Evidence from cell-free DNA analysis. J Heart Lung Transplant. 2018 Jul;37(7):925-932. doi: 10.1016/j.healun.2018.01.1305. Epub 2018 Jan 31.

    PMID: 29500138DERIVED

  • Vollmers C, De Vlaminck I, Valantine HA, Penland L, Luikart H, Strehl C, Cohen G, Khush KK, Quake SR. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study. PLoS Med. 2015 Oct 14;12(10):e1001890. doi: 10.1371/journal.pmed.1001890. eCollection 2015 Oct.

    PMID: 26466143DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

A single whole blood specimen from both the donor and recipient of the organ prior to transplant. Additionally, blood samples are taken post-transplant at specified timepoints and spun down into a plasma, buffycoat layer. The plasma and buffycoat are retained while the rest is discarded.

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social BehaviorBehavior

Study Officials

  • Kiran Khush, MD MAS FACC

    Stanford University Hospital and Clinics

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Kiran Khush, MD, MAS, FACC

Study Record Dates

First Submitted

May 28, 2013

First Posted

November 15, 2013

Study Start

March 1, 2010

Primary Completion

September 29, 2013

Study Completion

September 29, 2013

Last Updated

October 4, 2019

Record last verified: 2019-10

Locations

US(2)