Clinical trial NCT00407160: A Trial of Tolerogenic Immunosuppression in Highly Sensitized Renal Transplant Recipients
Official title: Comparison of Two Different Immunosuppression Protocols in Highly Sensitized Renal Transplant Recipients: Campath Induction With Tacrolimus Monotherapy vs Thymoglobulin Induction With Triple Drug Protocol.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Diseases
Keywords: Kidney transplant
Tolerance induction
High Panel Reactive Antibody (PRA) kidney recipients
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2006-12-04
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with end stage renal disease , on dialysis, who are regarded as "high immunological risk" becuase they have lost previous transplants to rejection, or have a high panel reactive antibody (PRA).

Brief summary: Comparison between Campath induction and monotherapy with Tacrolimus vs Thymoglobulin induction and triple drug maintenance using Tacrolimus, mycophenolate, and steroids.

Detailed description: Recent reports suggest that it might be possible to induce a state of tolerance in solid organ transplantation. So called "tolerogenic immunosuppression" involves induction with lymphocyte depleting antibodies followed by monotherapy with calcineurin inhibitors, cyclosporin or tacrolimus. The proposed study aims to evaluate a protocol of immunosuppression induction with lymphocyte depleting antibody Campath given prior to graft reperfusion, followed by tacrolimus monotherapy in highly sensitized patients (PRA \>14% or past historical =/\>50% and/or multiple renal transplants) undergoing renal transplantation, and compare it with the current standard protocol at UTMB which employs induction with Thymoglobulin given over 4 days followed by 3 drugs: tacrolimus, mycophenolate and steroids. In both groups of patients the target tacrolimus levels will be the same i.e, between 10 to 15ng/mL, soon after the transplant. In the Campath gro up, tacrolimus will be tapered after 3 months in patients who do not have rejection and appear to be developing donor specific tolerance.

Eligibility criteria: Inclusion Criteria:

1. Males and females aged 18-75 years.
2. Recipients of multiple kidney transplants
3. Patients with a PRA \>14% and/or a past historical PRA greater or equal to 50%.
4. Females of childbearing potential must have a negative pregnancy test prior to inclusion.
5. Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.

Exclusion Criteria:

1. Patients with a history of malignancy within the last 5 years, except excised squamous or basal cell carcinoma of the skin.
2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation,confirmed by a positive human chorionic gonadotropin(hCG) laboratory test.
3. Patients who are HIV positive.
4. Patients with symptoms of significant somatic or mental illness or evidence of current drug and/or alcohol abuse.

Primary outcomes:
measure: graft survival
timeFrame: 1 year
Secondary outcomes:
measure: rejection episodes
timeFrame: 1 year
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: UTMB Department of Surgery
name: Philip G Thomas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Calne RY. Prope tolerance: a step in the search for tolerance in the clinic. World J Surg. 2000 Jul;24(7):793-6. doi: 10.1007/s002680010127.
citation: Magliocca JF, Knechtle SJ. The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transpl Int. 2006 Sep;19(9):705-14. doi: 10.1111/j.1432-2277.2006.00343.x.
citation: Thomas PG, Woodside KJ, Lappin JA, Vaidya S, Rajaraman S, Gugliuzza KK. Alemtuzumab (Campath 1H) induction with tacrolimus monotherapy is safe for high immunological risk renal transplantation. Transplantation. 2007 Jun 15;83(11):1509-12. doi: 10.1097/01.tp.0000263344.53000.a1.