Transplant SensitizationNCT01334281
An In-vitro Standardization of B Cell Elispot Assays
An observational study of Transplant Sensitization and Panel Reactive Antibody, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transplant Sensitization, Panel Reactive Antibody, Sensitization to HLA Antigens
- What is being tested?
- Blood Draw
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Oct 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Subjects younger than 18 years of age
- Subjects with no sensitization history
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern Memorial Hospital
Chicago, Illinois, 60611
About this study
Official title: A Phase 1, Investigatory Initiated, In-vitro Standardization of B Cell Elispot Assays
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.
Read the 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.
- Being tested
- Blood Draw
- Keywords
- Panel Reactive Antibody (PRA), Sensitization, Organ Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood DrawProcedure or surgery
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 DrawProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Blood Draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
B cells will be tested unstimulalated or stimulated with a cocktail of CpG, anti-CD40-L, IL-10 and IL-4.
Measured: Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2011 (estimated)
- Study startFeb 2008
- Primary completionApr 2011
- Study completionOct 2012
Why it stopped: Technical difficulties perfecting laboratory test used on blood samples.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transplant SensitizationStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anat Tambur, Northwestern University
- Investigators
- Anat Tambur, DMD, PhD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01334281
- Sponsor's protocol ID
- STU00027653 1682-05
- Other IDs
- 0037-370-285V-AT
- Status last verified
- Apr 2013
- First submitted
- 13 Apr 2009
- Last updated
- 22 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Investigatory Initiated, In-vitro Standardization of B Cell Elispot Assays
- ClinicalTrials.gov ID
- NCT01334281
- Acronym / sponsor ID
- STU00027653 1682-05
- Keywords
- Panel Reactive Antibody (PRA), Sensitization, Organ Transplant
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Technical difficulties perfecting laboratory test used on blood samples.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Feb 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 13 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Blood: Undergoing Desensitization | – | Procedure: Blood DrawTransplant 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. |
| Blood: NOT Undergoing Desensitization | – | Procedure: Blood DrawTransplant 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- Subjects younger than 18 years of age
- Subjects with no sensitization history
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood DrawThree 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. | Procedure or surgery | Blood: Undergoing Desensitization |
| Blood DrawThree 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. | Procedure or surgery | Blood: NOT Undergoing Desensitization |
Primary outcome
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.
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).
1 secondary outcome
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.
Results and safety
The study was stopped early (reason given: Technical difficulties perfecting laboratory test used on blood samples.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anat Tambur, DMD, PhD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Transplant Sensitization and Panel Reactive Antibody, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Technical difficulties perfecting laboratory test used on blood samples.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2013.