Prospective Donor Specific Antibody (DSA) Monitoring Protocol

Kidney Transplant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01382355
• Other study ID #: PDSAM 011
• Status: Recruiting
• Phase: N/A
• First received: June 21, 2011
• Last updated: August 2, 2011
• Start date: August 2011
• Est. completion date: August 2012

Study information

• Verified date: August 2011
• Source: Providence Health & Services
• Contact: Angela Q Maldonado, PharmD
• Phone: 5094746993
• Email: angela.maldonado[@]providence.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• Have not received a transplant

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Kidney Transplant
• Kidney/Pancreas Transplant

Locations

Country	Name	City	State
United States	Providence Sacred Heart Medical Center	Spokane	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Providence Health & Services	Paul I Terasaki Foundation Laboratory, Washington State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who develop DSA within the first year post-transplant		1 year	No
Primary	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	No
Secondary	Change in allograft function at 1 year post-transplant compared to baseline (measured by Cockcroft-Gault)		1 year	No
Secondary	Incidence of patient survival at 1 year		1 year	No
Secondary	Proportion of patients who are DSA negative at 1 year		1 year	No
Secondary	Percent change of DSA from baseline to 1 year		1 year	No
Secondary	Proportion of Class I versus Class II detectable DSA that progress to antibody mediated rejection		1 year	No
Secondary	Incidence of allograft survival at 1 year		1 year	No