An In-vitro Standardization of B Cell Elispot Assays

NCT01334281 | Terminated

• 2 other identifiers: STU00027653 1682-050037-370-285V-AT
• Study Type: observational
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done because the study doctor is trying to develop a new test which will help transplant doctors monitor patients with high panel reactive antibodies (PRA). The test would be used to monitor patients' PRA when doctors are trying to lower it through a process known as desensitization. Desensitization lowers high PRA levels and allows patients to receive transplants. This is a single center study to evaluate and optimize the use of a new laboratory test to detect and measure the immune system's functioning.

Conditions

Transplant Sensitization; Panel Reactive Antibody; Sensitization to HLA Antigens

Keywords

Panel Reactive Antibody (PRA); Sensitization; Organ Transplant

Outcome Measures

Primary Outcomes (1)

• To optimize an in-vitro assay to enumerate HLA-specific memory B cells in order to monitor efficacy of desensitization protocols.

  B cells will be tested for their ability to produce IgG and tetanus antibodies (as controls) and HLA specific antibodies corresponding to those detected by the flow PRA assay. In subjects not undergoing desensitization, 3 tubes (30 ml) of blood will be drawn twice (total of 60 ml blood taken) 8-12 weeks apart. In subjects undergoing desensitization 3 tubes (30 ml) of blood will be taken at 7 points; enrollment, anticipated midpoint of desensitization, prior to transplant, 3, 6, 12 and 24 Months post-transplant (total of 210 ml blood taken).

  Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.

Secondary Outcomes (1)

• Evaluate the relationships between antibody strength, measured by flow cytometry, number of memory B cells in circulation of highly sensitized patients awaiting organ transplant or undergoing desensitization procedures to facilitate organ transplant.

  Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.

Study Arms (2)

Blood: Undergoing Desensitization

Transplant subjects give blood at specified time points. Sensitization to HLA antigens is a barrier to transplant. Several U.S. institutions have protocols for desensitization where patients are treated with IV immunoglobulins (IVIg) and plasmapheresis (PP) to reduce circulating HLA-directed antibody levels. Labs provide doctors information on circulating donor-specific antibody (DSA) levels. These results are the main indicator whether to proceed with transplant. However, no information is given on the fate of the B cells that produce the DSA.

Procedure: Blood Draw

Blood: NOT Undergoing Desensitization

Transplant subjects give blood at specified time points. Sensitization to HLA antigens is a barrier to transplant. Several U.S. institutions have protocols for desensitization where patients are treated with IV immunoglobulins (IVIg) and plasmapheresis (PP) to reduce circulating HLA-directed antibody levels. Labs provide doctors information on circulating donor-specific antibody (DSA) levels. These results are the main indicator whether to proceed with transplant. However, no information is given on the fate of the B cells that produce the DSA.

Procedure: Blood Draw

Interventions

Blood Draw PROCEDURE

Three tubes of blood will be drawn (three 10ml-green top), 7 times (total of 210 ml for study) at the indicated time points: 1) enrollment, 2) anticipated midpoint of desensitization, 3) prior to transplant, 4) three months post-transplant, 5) six months post-transplant, 6) 12 months post-transplant, and 7) 24 months post-transplant.

Blood: Undergoing Desensitization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any kidney, pancreas or heart transplant waitlisted subjects \> or = to 18 years of age, and of either gender. Subjects must be capable of understanding the study, informed consent form, HIPPA process, and be willing to give informed consent.

You may qualify if:

• Subjects should be listed for solid organ transplant at NU/NMH
• Subjects should be \> or = to 18 years of age, either gender
• Subjects should have history of prior sensitization of HLA antigens
• Subjects should have documented antibody specificity previously tested at the transplant immunology lab at NU
• Subjects should be capable of understanding the study, consents, HIPAA process and be able to give informed consent.

You may not qualify if:

• Subjects younger than 18 years of age
• Subjects with no sensitization history

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Subjects will serve as a source of B-lineage cells, which will be tested for their ability to produce IgG, tetanus antibodies, (as controls) and HLA specific antibodies that coorespond to those detected by the flow PRA assay. They will be retained until they are used up.

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Anat Tambur, DMD, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Transplant Immunology Laboratory, Comprehensive Transplant Center; Research Professor, Feinberg School of Medicine

Study Record Dates

• First Submitted: April 13, 2009
• First Posted: April 13, 2011
• Study Start: February 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: October 1, 2012
• Last Updated: April 22, 2013

Record last verified: 2013-04

Locations

US (1)