Biomarkers in Transplant Recipients to Improve Outcomes

Study of Biomarkers in Solid Organ and Bone Marrow Transplant Recipients to Better Treat Rejection

The objective of this study is to evaluate whether certain proteins, expressed in biological tissues can indict a better understanding of the effect of drugs that are used to treat rejection, and of processes leading to rejection and rejection-free outcomes.

Study Overview

• Status: Recruiting
• Conditions: Bone Marrow Transplantation; Solid Organ Transplantation

Detailed Description

All transplant recipients receive periodic monitoring of drug levels and laboratory tests to assess adequacy of immunosuppression and allograft function. These are performed when the recipient is admitted to the hospital after transplantation or for a complication such as acute rejection or toxicity, or when the recipient is an outpatient.

1. Blood samples: Participants may be asked to provide research blood specimens during regular clinical tests, and may collect up to 15 milliliters of blood as many as 7 times within the first year of transplant, and then less often thereafter. The total volume collected will take in account the patient's height, weight and age at the time of the collection. However, if for any reason participant is unable to provide a sample during regular clinical test it may be collected at another time. Participants will be asked to provide these samples indefinitely. This will allow longitudinal assessment of the stability of biomarker expression as a reflection of clinical drug concentrations in repeated measurements.
2. Saliva collection: Up to 5 ml of the subject's saliva will be collected no more than four times, if the previous sample does not provide adequate information. Samples will be collected in self-collection container at the time of consent or as early as possible after consents are obtained, and will be stored at room temperature in the Pediatric Transplantation Laboratory, 3344 Forbes Ave. In recipients where both are available, the genotyping results as DNA from saliva will be compared between paired blood samples. Henceforth, saliva collection will only be offered to participants who cannot donate blood specimens for genotyping. Salivary sampling is considered an acceptable alternative standard for whole blood genotyping. A saliva sample will be collected only if the patient or the patient's parent or guardian prefers this option over blood sampling.
3. Collection of urine, feces, and bile: five mls of any body fluid will be collected in sterile urine cups for application of proteomics technologies. Collections may be repeated up to four times, if the first specimen provides suboptimal information.
4. Collection of remaining allograft standard of care biopsy specimens, and tissue from explants: Any piece of allograft biopsy deemed residual by the pathologist will be subjected to gene array testing. This will occur when participant is scheduled for their standard of care biopsy, or while in surgery. Genetic material extracted from the smallest tissue can be amplified using several approaches.
5. Measurements: Biomarker expression will be evaluated after mitogen and antigen stimulation of peripheral blood mononuclear cells. (1-3). Briefly, peripheral blood mononuclear cells (PBMC) are extracted from whole blood by Ficoll gradient separation, Thereafter, either mitogens such as phytohemaglutinin, pokeweed mitogen, or phorbol-myristic acid-ionomycin, or viral and major histocompatibility complex (MHC) peptide antigens, or intact alloantigenic cells will be used to stimulate recipient PBMC. Cellular responses that can be measured include but are not limited to expressed pro-inflammatory or anti-inflammatory markers, cytokines, proliferation, cytotoxicity, and apoptosis.

• Study Type: Observational
• Enrollment (Estimated): 1200

Contacts and Locations

• Study Contact: Name: Daniel Pieratt, MPA; Phone Number: 412-692-6692; Email: pierattdw@upmc.edu
• Study Contact Backup: Name: Morgan L Paul, BSN; Phone Number: 412-692-8472; Email: Morgan.Paul2@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Children's Hospital of Pittsburgh of UPMC
      • Contact: Daniel Pieratt, MPA; Phone Number: 412-692-6692; Email: pierattdw@upmc.edu
      • Contact: Morgan L Paul, BSN; Phone Number: 412-692-8472; Email: Morgan.Paul2@upmc.edu
      • Principal Investigator: Rakesh Sindhi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals who are listed and or recipients of solid organ or bone marrow transplantation.

Description

Inclusion Criteria:

• Recipients of abdominal, thoracic and bone marrow allografts that are receiving inpatient and outpatient follow-up with routine laboratory tests at the University of Pittsburgh Medical Center.
• All Ages
• Subject or parents are able to read and understand the informed consent

Exclusion Criteria:

• Subjects and/or their parents who are unable to read and understand informed consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rejection	Biopsy-proven acute cellular rejection	90 day post transplantation (clinical severity)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thresholds of immunosuppression	Blood levels and doses of the various immunosuppressants at one year. For example, Tacrolimus is measured as nanograms/ml in whole blood, Mycophenolate mofetil is measured in doses of mg/day, or as blood levels in micrograms/ml, steroids doses are measured in mg/day, Sirolimus is measured in doses of mg/day, or as blood levels in nanograms/ml in whole blood.	Yearly post transplantation

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Rakesh Sindhi, MD, University of Pittsburgh

Publications and helpful links

General Publications

• Ashokkumar C, Sun Q, Ningappa M, Higgs BW, Mazariegos G, Zeevi A, Sindhi R. Antithymocyte globulin facilitates alloreactive T-cell apoptosis by means of caspase-3: potential implications for monitoring rejection-free outcomes. Transplantation. 2015 Jan;99(1):164-70. doi: 10.1097/TP.0000000000000289.
• Ashokkumar C, Gabriellan A, Ningappa M, Mazariegos G, Sun Q, Sindhi R. Increased monocyte expression of sialoadhesin during acute cellular rejection and other enteritides after intestine transplantation in children. Transplantation. 2012 Mar 15;93(5):561-4. doi: 10.1097/TP.0b013e3182449189.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: June 29, 2010
• First Submitted That Met QC Criteria: July 14, 2010
• First Posted (Estimated): July 15, 2010

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Rejection; Transplantation
• Additional Relevant MeSH Terms: Behavior; Social Behavior; Rejection, Psychology
• Other Study ID Numbers: STUDY19030279