Prospective Donor Specific Antibody (DSA) Monitoring Protocol

Prospective Donor Specific Antibody (DSA) Monitoring Protocol To Detect Patient Characteristics and /or Changes In Immunosuppression on the Development of De Novo Antibodies

Advances in transplant pharmacotherapy have led to improved one-year patient and graft survival in kidney transplant recipients, but have not translated to enhanced long-term survival. An explanation for the disparity in outcomes is the negative role of antibodies in transplant graft survival. There currently does not exist maintenance immunosuppression that targets antibodies and standard of practice aims at removing circulating donor specific antibodies upon detection of antibody mediated graft damage but not prior to the detection of rejection. There exists an insufficiency of data regarding patient and donor characteristics, changes in immunosuppression, the risk of viral donor and patient seropositivity and the risk of non-compliance on the development of antibodies. By measuring antibody levels in the blood at specific time periods after transplant, we may have a better understanding of what types of patients will develop antibodies, when these antibodies appear and how changes to transplant medications may affect antibodies.

The proposed project will examine the multifactorial risks associated with the development and appearance of donor-specific antibodies in the first year post-kidney transplant. The data collected will provide a historical perspective and preliminary pilot data to support a proposal for prospective antibody monitoring and to justify pre-emptively treating the antibodies in the absence of clinical signs of rejection.

Study Overview

• Status: Unknown
• Conditions: Kidney Transplant; Kidney/Pancreas Transplant

Detailed Description

Organ transplantation is an effective treatment for several end-stage organ diseases. Preventing rejection of transplanted organs remains the premier challenge. According to the humoral theory, donor specific antibodies (DSA) are the major cause of chronic rejection and allograft loss. Despite this, and evidence that links human leukocyte antigen (HLA) antibodies to allograft dysfunction and loss, doubt remains about the cause-and-effect relationship and confirmation of this evidence is necessary to help facilitate change in transplant practice. Prospective monitoring for de novo DSA in the serum of patients who have received a transplant may allow for earlier detection, evaluation, and characterization of factors leading to the development of antibodies prior to the development of clinical manifestations of graft dysfunction.

The contribution of the major histocompatibility complex (MHC) Class I and Class II antibodies to transplant outcomes is well documented. However, there is emerging evidence that antibody mediated rejection and the severity of outcomes may involve proteins and antibodies that go beyond HLA Class I and II. A number of assays are available for testing for these additional antibodies and proteins but they are currently not used for widespread patient monitoring in part due to lack of data justifying their commercial use. This pilot study will prospectively evaluate for the presence and/or emergence of these unique antibodies, (I.E. MICA antigen, IgG3 and C1Q) in serial samples of serum, and confirm or reject the utility of incorporating these assays into routine patient monitoring which might provide earlier evidence of emerging rejection. Serum samples will be stored indefinitely for future kidney transplant research projects.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Angela Q Maldonado, PharmD; Phone Number: 5094746993; Email: angela.maldonado@providence.org
• Study Contact Backup: Name: Beth C Aaron, CCRC; Phone Number: 5092306001; Email: beth.aaron@providence.org

Study Locations

• United States
  • Washington
    • Spokane, Washington, United States, 99204
      • Recruiting
      • Providence Sacred Heart Medical Center
      • Contact: Beth C Aaron, CCRC; Phone Number: 5092306001; Email: beth.aaron@providence.org
      • Contact: Angela Q Maldonado, PharmD; Phone Number: 509-474-6993; Email: angela.maldonado@providence.org
      • Sub-Investigator: Matthew J Everly, PharmD
      • Sub-Investigator: Okechukwu N Ojogho, MD
      • Sub-Investigator: Richard W Carson, MD
      • Sub-Investigator: Beth C Aaron, CCRC
      • Sub-Investigator: Sara Desmond, ARNP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Males and females aged 18-70 years old receiving a living donor or deceased donor kidney or kidney/pancreas transplant

Description

Inclusion Criteria:

• Have received a living donor or deceased donor kidney/kidney pancreas transplant

Exclusion Criteria:

• Have not received a transplant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Kidney transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who develop DSA within the first year post-transplant		1 year
Risk factors for developing DSA	Patient demographics and immunosuppression regimen to be collected: Age at transplant Date of transplant Gender Race Cause of renal failure Donor type Repeat transplant (yes/no) Transplant current panel reactive antibody (PRA) Transplant flow crossmatch Previous crossmatch Serum creatinine at baseline DSA Class I/Class II, MICA, IgG3, C1Q Induction and maintenance immunosuppressant therapy Cytomegalovirus, BK virus, and Epstein Barr virus patient and donor seropositivity	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in allograft function at 1 year post-transplant compared to baseline (measured by Cockcroft-Gault)	1 year
Incidence of patient survival at 1 year	1 year
Proportion of patients who are DSA negative at 1 year	1 year
Percent change of DSA from baseline to 1 year	1 year
Proportion of Class I versus Class II detectable DSA that progress to antibody mediated rejection	1 year
Incidence of allograft survival at 1 year	1 year

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Washington State University; Paul I Terasaki Foundation Laboratory
• Investigators: Principal Investigator: Angela Q Maldonado, PharmD, Providence Sacred Heart Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): August 1, 2012
• Study Completion (Anticipated): August 1, 2012

Study Registration Dates

• First Submitted: June 21, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): August 4, 2011
• Last Update Submitted That Met QC Criteria: August 2, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Monitoring; Antibody; Kidney transplant; Kidney/Pancreas transplant
• Other Study ID Numbers: PDSAM 011