Prospective Donor Specific Antibody (DSA) Monitoring Protocol

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by Providence Health & Services.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Washington State University
Paul I Terasaki Foundation Laboratory
Information provided by:
Providence Health & Services
ClinicalTrials.gov Identifier:
NCT01382355
First received: June 21, 2011
Last updated: August 2, 2011
Last verified: August 2011
  Purpose

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
Kidney Transplant
Kidney/Pancreas Transplant

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Providence Health & Services:

Primary Outcome Measures:
  • Proportion of patients who develop DSA within the first year post-transplant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Risk factors for developing DSA [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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:
  • Change in allograft function at 1 year post-transplant compared to baseline (measured by Cockcroft-Gault) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Incidence of patient survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Proportion of patients who are DSA negative at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Percent change of DSA from baseline to 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Proportion of Class I versus Class II detectable DSA that progress to antibody mediated rejection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Incidence of allograft survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

1 ml aliquots of serum collected at specified time points


Estimated Enrollment: 60
Study Start Date: August 2011
Estimated Study Completion Date: August 2012
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Kidney 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Have not received a transplant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01382355

Contacts
Contact: Angela Q Maldonado, PharmD 5094746993 angela.maldonado@providence.org
Contact: Beth C Aaron, CCRC 5092306001 beth.aaron@providence.org

Locations
United States, Washington
Providence Sacred Heart Medical Center Recruiting
Spokane, Washington, United States, 99204
Contact: Angela Q Maldonado, PharmD    509-474-6993    angela.maldonado@providence.org   
Contact: Beth C Aaron, CCRC    5092306001    beth.aaron@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         
Sponsors and Collaborators
Providence Health & Services
Washington State University
Paul I Terasaki Foundation Laboratory
Investigators
Principal Investigator: Angela Q Maldonado, PharmD Providence Sacred Heart Medical Center
  More Information

No publications provided

Responsible Party: Angela Maldonado PharmD, BCPS/Clinical Assistant Professor/Transplant Pharmacist, Providence Sacred Heart Medical Center
ClinicalTrials.gov Identifier: NCT01382355     History of Changes
Other Study ID Numbers: PDSAM 011
Study First Received: June 21, 2011
Last Updated: August 2, 2011
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014