Prospective Donor Specific Antibody (DSA) Monitoring Protocol

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01382355
Recruitment Status : Unknown
Verified August 2011 by Providence Health & Services.
Recruitment status was:  Recruiting
First Posted : June 27, 2011
Last Update Posted : August 4, 2011
Washington State University
Paul I Terasaki Foundation Laboratory
Information provided by:
Providence Health & Services

Brief 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.

Condition or disease
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
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Study Start Date : August 2011
Estimated Primary Completion Date : August 2012
Estimated Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

Kidney transplant

Primary Outcome Measures :
  1. Proportion of patients who develop DSA within the first year post-transplant [ Time Frame: 1 year ]
  2. Risk factors for developing DSA [ Time Frame: 1 year ]

    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

Secondary Outcome Measures :
  1. Change in allograft function at 1 year post-transplant compared to baseline (measured by Cockcroft-Gault) [ Time Frame: 1 year ]
  2. Incidence of patient survival at 1 year [ Time Frame: 1 year ]
  3. Proportion of patients who are DSA negative at 1 year [ Time Frame: 1 year ]
  4. Percent change of DSA from baseline to 1 year [ Time Frame: 1 year ]
  5. Proportion of Class I versus Class II detectable DSA that progress to antibody mediated rejection [ Time Frame: 1 year ]
  6. Incidence of allograft survival at 1 year [ Time Frame: 1 year ]

Biospecimen Retention:   Samples With DNA
1 ml aliquots of serum collected at specified time points

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Inclusion Criteria:

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

Exclusion Criteria:

  • Have not received a transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01382355

Contact: Angela Q Maldonado, PharmD 5094746993
Contact: Beth C Aaron, CCRC 5092306001

United States, Washington
Providence Sacred Heart Medical Center Recruiting
Spokane, Washington, United States, 99204
Contact: Angela Q Maldonado, PharmD    509-474-6993   
Contact: Beth C Aaron, CCRC    5092306001   
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         
Sponsors and Collaborators
Providence Health & Services
Washington State University
Paul I Terasaki Foundation Laboratory
Principal Investigator: Angela Q Maldonado, PharmD Providence Sacred Heart Medical Center

Responsible Party: Angela Maldonado PharmD, BCPS/Clinical Assistant Professor/Transplant Pharmacist, Providence Sacred Heart Medical Center Identifier: NCT01382355     History of Changes
Other Study ID Numbers: PDSAM 011
First Posted: June 27, 2011    Key Record Dates
Last Update Posted: August 4, 2011
Last Verified: August 2011

Keywords provided by Providence Health & Services:
Kidney transplant
Kidney/Pancreas transplant

Additional relevant MeSH terms:
Immunologic Factors
Physiological Effects of Drugs