- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01334281
An In-vitro Standardization of B Cell Elispot Assays
A Phase 1, Investigatory Initiated, In-vitro Standardization of B Cell Elispot Assays
Study Overview
Status
Intervention / Treatment
Detailed Description
Sensitization to HLA antigens is the main barrier to solid organ transplantation. Currently, HLA sensitization is monitored by testing patients' serum against a panel of HLA antigens (whether those will be presented on cell surface or on solid phase matrixes) and calculating the % of positive responses. Such result give indication of the relative breadth of sensitization but not on it "depth" - the relative strength of specific antibodies, nor does it provide any information regarding the memory B cells / plasma cells that can manufacture a specific HLA directed antibody.
This is a single center study to evaluate and optimize the use of in-vitro assay to enumerate B cells producing human leukocyte antigens (HLA)-specific antibodies. The proposed assay is based on principles used for enumeration of specific cytokine producing memory T cells - an ELISPOT assay. The investigators are currently using the T cell ELISPOT assay in our laboratory.
The investigators believe that the proposed assay will provide biologically relevant immune measures that are crucial for the long term outcome of transplantation in highly sensitized patients.
Highly sensitized patients encompass a high risk patient group among transplant recipients. The proposed assay is designed to predict the fate of DSA producing (or capable of producing) memory and plasma cells. Thus, it should allow prediction and early detection of activation of the humoral arm of the immune system, specifically against the donor. This, in turn, may prompt early intervention and preservation of the allograft. Three tubes of blood will be drawn twice, 8-12 weeks apart, during clinic or standard of care dialysis visits following optimization. Subjects undergoing desensitization will have three tubes of blood drawn seven times over the course of two years for the analysis.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Illinois
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Chicago, Illinois, United States, 60611
- Northwestern Memorial Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Subjects younger than 18 years of age
- Subjects with no sensitization history
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
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.
Three tubes of blood will be drawn (three 10ml-green top) twice (60 ml total for study), 8-12 weeks apart.
Can be drawn during clinic visit or separate standard of care dialysis visit.
|
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.
|
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.
Three tubes of blood will be drawn (three 10ml-green top) twice (60 ml total for study), 8-12 weeks apart.
Can be drawn during clinic visit or separate standard of care dialysis visit.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To optimize an in-vitro assay to enumerate HLA-specific memory B cells in order to monitor efficacy of desensitization protocols.
Time Frame: Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.
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B cells will be tested unstimulalated or stimulated with a cocktail of CpG, anti-CD40-L, IL-10 and IL-4.
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Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Anat Tambur, DMD, PhD, Northwestern University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- STU00027653 1682-05
- 0037-370-285V-AT (Other Identifier: Northwestern University Internal Tracking Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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