Kidney Transplant
Conditions
Brief summary
The purpose of this study is to check the T and B cells of the immune system in 50 newly transplanted patients whom have received a kidney (50 recipients and 50 donors totaling 100 anticipated participants). This will be done to see how the Standard of Care (SOC) anti-rejection medication, Alemtuzumab (Campath 1-H®) affects these cells- Campath 1-H® reduces the number of T cells produced by one's body.
Detailed description
The purpose of this study is to check the T and B cells of the immune system in 50 newly transplanted patients whom have received a kidney (50 recipients and 50 donors totaling 100 anticipated participants). This will be done to see how the Standard of Care (SOC) anti-rejection medication, Alemtuzumab (Campath 1-H®) affects these cells- Campath 1-H® reduces the number of T cells produced by one's body. We will look for these cells using a number of laboratory tests; It will require the subjects to each give 65mL of blood at each of the 3 visits that occur during phase 1. Up to 12 subjects will be chosen from phase 1 to participate in phase 2 depending on lab results. In phase 2, subjects will be randomized to one of the three following groups: Group one: Continue normal immunosuppression with tacrolimus and Cellcept® (control group) Group two: Cellcept® will be tapered down to 70% in three months. Tacrolimus will be continued at the same dosage. Group three: Tacrolimus will be reduced to 70% in three months. Cellcept® will be continued at the same dosage. There will be an analysis of these cells at different time point, pre and post kidney transplant. The data collection will allow us to study the stability over time of particular phenotypes (cell structures) and T cell function. We will also evaluate how the two different minimizing protocols effect the cell structure. Results from laboratory testing may allow us to define certain criteria that can be broadly applied in solid organ transplant recipients. This may allow for safe reduction of the anti-rejection medication that transplant recipients receive.
Interventions
DRUGAlemtuzumab
All kidney transplant recipients received one 30mg dose (IV push) of Alemtuzumab in operating room per Standard of Care.
Sponsors
Northwestern University
American Society of Transplant Surgeons
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1: 50 subjects were to receive study intervention. If any subjects demonstrated persistent donor specific unresponsiveness at the 12 month post-transplant time point, they would proceed into Phase 2. In that phase, the unresponsive subjects would have been randomized to one of three arms that would modify their standard of care immunosuppression. None of the 50 subjects from Phase 1 demonstrated persistent donor specific unresponsiveness, therefore, phase 2 was never started.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adult subjects between ages 18-65 years old of either gender 2. Recipients have an available ABO compatible living donor for transplant 3. Subjects are listed to be a single-organ transplant recipient (kidney only) 4. Subjects have the ability to provide informed consent
Exclusion criteria
1. Subjects have panel reactive antibody greater than 35% 2. Subjects have the potential to have a high recurrence rate of their primary renal disease (i.e. Focal Segmental Glomerulonephritis ) 3. Subjects who have a history of Hepatitis C 4. Subjects who have had a previous organ transplant 5. Subjects are unable to fully understand the purpose of the study, thereby unable to give a fully informed consent 6. Subjects with a positive lymphocytotoxic crossmatch using donor lymphocytes and recipient serum 7. Subjects who are pregnant or nursing 8. Subjects who, due to the existence of a surgical, medical or psychiatric condition, other than the current transplant, which in the opinion of the investigator, precludes enrollment into this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of T Cell Depletion on Phenotypic & Functional Profiles of Peripheral Blood Mononuclear Cells in Steroid-free Kidney Transplant Recipients. | Pre-transplant, 6months & 12 months post-transplant | Blood was collected to assess peripheral blood leukocytes prior to kidney transplant, 6 months & 12 months post-transplant as follows: to obtain absolute count of circulating CD4, CD8 positive T cells, B cells & NK cells, naive & memory cells (CD45RA, CD45RO), activated T cells (CD4/CD38, CD8/CD38), regulatory cells (CD4+ CD25+). Unfortunately blood samples were lost due to malfunction of liquid nitrogen tank that stopped working during a power loss. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Donor Specific Hypo-reactivity. | Pre-transplant, 6mo & 12mo post-transplant | Identify, by studying recipients for development of donor specific hypo-reactivity and through immunopathologic analysis of renal allograft biopsies, immunologically stable renal transplant patients in whom immunosuppression can be safely minimized. Unfortunately this secondary outcome was not studied because of lost samples that did not allowed us further analysis to identify patients with donor specific hypo reactivity. |
Countries
United States
Participant flow
Recruitment details
All patients were approached pre-operatively in the transplant clinic at Northwestern Memorial Hospital. Recruitment began on July 28, 2005 and lasted until April 14, 2008.
Pre-assignment details
The first year of the study was specimen collection only. Group assignment (phase 2) was intended to begin after 12months of sample collection and there were not any subjects who continued into phase 2. An additional pair enrolled compared to the number that started this study. This is due to a loss of samples from a processing inconsistency
Participants by arm
| Arm | Count |
|---|---|
| Alemtuzumab (Phase I) All transplant recipients received one 30mg dose (intravenous IV push)of Alemtuzmab in the operating room per Standard of Care. | 26 |
| Donor Comparison | 25 |
| Total | 51 |
Baseline characteristics
| Characteristic | Total | Alemtuzumab (Phase I) | Donor Comparison |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 26 Participants | 25 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 31.46 | 41 years STANDARD_DEVIATION 22 | 43 years STANDARD_DEVIATION 9.46 |
| Region of Enrollment United States | 51 participants | 26 participants | 25 participants |
| Sex: Female, Male Female | 18 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 33 Participants | 21 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 25 |
| serious Total, serious adverse events | 0 / 26 | 0 / 25 |
Outcome results
Primary
The Effect of T Cell Depletion on Phenotypic & Functional Profiles of Peripheral Blood Mononuclear Cells in Steroid-free Kidney Transplant Recipients.
Blood was collected to assess peripheral blood leukocytes prior to kidney transplant, 6 months & 12 months post-transplant as follows: to obtain absolute count of circulating CD4, CD8 positive T cells, B cells & NK cells, naive & memory cells (CD45RA, CD45RO), activated T cells (CD4/CD38, CD8/CD38), regulatory cells (CD4+ CD25+). Unfortunately blood samples were lost due to malfunction of liquid nitrogen tank that stopped working during a power loss.
Time frame: Pre-transplant, 6months & 12 months post-transplant
Population: samples from 26 recipient/donor pairs were collected = 52 collected but no analysis was performed because samples were lost.
Secondary
Donor Specific Hypo-reactivity.
Identify, by studying recipients for development of donor specific hypo-reactivity and through immunopathologic analysis of renal allograft biopsies, immunologically stable renal transplant patients in whom immunosuppression can be safely minimized. Unfortunately this secondary outcome was not studied because of lost samples that did not allowed us further analysis to identify patients with donor specific hypo reactivity.
Time frame: Pre-transplant, 6mo & 12mo post-transplant
Population: no one were analyzed due to loss of blood samples