Clinical trial NCT00466804: Noninvasive Methods to Monitor Graft Survival in Heart Transplant Patients
Official title: Observational Study of Alloimmunity in Cardiac Transplant Recipients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Transplant
Keywords: heart transplant recipients
organ transplantation
immune biomarkers
transplant rejection
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Clinical Trials in Organ Transplantation
First posted: 2007-04-27
Enrollment: 263
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People who are on the waiting list for a heart transplant at one of the participating study sites (listed below)

Brief summary: Injury of transplant tissue by a transplant recipient's immune system continues to be the leading cause of graft rejection and recipient death. The purpose of this study is to identify a single test or a combination of noninvasive tests currently used for heart transplant monitoring that correlate to long-term graft survival.

Detailed description: A major cause of heart transplant failure is the blockage of blood flow from lesions caused by ongoing injury and repair of the graft by the host's immune system. However, the role of T cells, antibodies, and other parts of the recipient's immune system are not well understood in transplant injury. Currently, there are no effective, noninvasive ways to detect or predict how an individual's immune system will react to a transplant. The purpose of this study is to correlate current noninvasive monitoring tests with long-term graft survival and function, and determine which tests are the most accurate predictors of this survival.

Participants in this study must currently be on the waiting list for a heart transplant and have a donor heart available to them. This study will consist of six study visits over 12 months. The baseline visit will occur on the day of transplantation. Follow-up visits will occur at Week 6 and Months 3, 6, 9, and 12 post-transplant. At each visit, a physical exam, medication tracking, assessment of graft survival, and blood and urine collection will occur. At the Week 6 and Month 12 visits, intravascular ultrasound and echocardiograms will occur. At the Week 6, Month 6, and Month 12 visits, endomyocardial biopsies will also occur. No immunosuppressive therapy will be provided by the study.

Eligibility criteria: Inclusion Criteria:

* Age greater than 10 and a body mass of 30 kg (66 lbs) or more
* On waiting list for a heart transplant for whom a donor heart available
* Willing to comply with study protocol
* Willing to use acceptable forms of contraception
* Parent or guardian willing to provide consent, if applicable

Exclusion Criteria:

* Receiving multiple organ transplants
* Previously received organ transplants
* Other comorbidities that, in the opinion of the site investigator, would interfere with the study
* Currently taking immunosuppression for nontransplant reasons
* Participation in an interventional clinical trial
* Pregnancy or breastfeeding

Primary outcomes:
measure: Composite Measure of Transplant Health
timeFrame: 12 months after enrollment in study
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California
state: California
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Maywood
country: United States
facility: Loyola University School of Medicine
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Newark
country: United States
facility: Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, LDS Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah, VACM.LDS
state: Utah
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Peter S. Heeger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Mohamed H. Sayegh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Randall Starling, MD
role: STUDY_CHAIR
References:
citation: Jiang S, Lechler RI. CD4+CD25+ regulatory T-cell therapy for allergy, autoimmune disease and transplant rejection. Inflamm Allergy Drug Targets. 2006 Dec;5(4):239-42. doi: 10.2174/187152806779010981.
citation: Starling RC, Pham M, Valantine H, Miller L, Eisen H, Rodriguez ER, Taylor DO, Yamani MH, Kobashigawa J, McCurry K, Marboe C, Mehra MR, Zuckerman A, Deng MC; Working Group on Molecular Testing in Cardiac Transplantation. Molecular testing in the management of cardiac transplant recipients: initial clinical experience. J Heart Lung Transplant. 2006 Dec;25(12):1389-95. doi: 10.1016/j.healun.2006.10.002. No abstract available.
citation: Zheng XX, Sanchez-Fueyo A, Sho M, Domenig C, Sayegh MH, Strom TB. Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance. Immunity. 2003 Oct;19(4):503-14. doi: 10.1016/s1074-7613(03)00259-0.
citation: Starling RC, Stehlik J, Baran DA, Armstrong B, Stone JR, Ikle D, Morrison Y, Bridges ND, Putheti P, Strom TB, Bhasin M, Guleria I, Chandraker A, Sayegh M, Daly KP, Briscoe DM, Heeger PS; CTOT-05 consortium. Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study. Am J Transplant. 2016 Jan;16(1):121-36. doi: 10.1111/ajt.13422. Epub 2015 Aug 10.