Clinical trial NCT01047865: Type 1 Diabetes Recurrence in Pancreas Transplants
Official title: Recurrence of T1D in Pancreas Transplantation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes Mellitus, Type 1
Keywords: Type 1 Diabetes (T1D)
Autoimmunity
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2010-01-13
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Type 1 diabetes who received a simultaneous pancreas-kidney (SPK) transplant

Brief summary: The hypothesis is that humoral and cellular islet-specific responses are an early risk factor for recurrence of autoimmunity and hyperglycemia in simultaneous pancreas-kidney (SPK) recipients independent of alloimmunity. This study will test the hypothesis and will assess their individual and combined predictive value.

Detailed description: To identify the factors associated with recurrence of diabetes in subjects who received a simultaneous pancreas-kidney (SPK) or pancreas transplant. The study will see if there are changes in the participant's blood that will help the investigator know whether diabetes has returned after the transplant.

SPK patients will be retrospectively analyzed to determine frequency, levels and time course of autoantibody recurrence and predictive value of autoantibodies for recurrence of the disease.

This study will prospectively follow our existing and our new pancreas transplant recipients to monitor autoantibody levels, monitor and phenotype autoreactive T cells in peripheral blood. This will happen monthly for 24 months.

This study will assess the presence or absence of insulitis in the transplanted pancreas from biopsies performed in recipients with consistent recurrence of multiple autoantibodies.

It will also monitor and phenotype autoreactive T cells from the pancreatic infiltrate obtained by pancreatic transplant biopsies.

Eligibility criteria: Inclusion Criteria:

* Patient has been fully informed and has signed a dated IRB approval informed consent form and is willing to follow study procedures for the extent of the study (24 months). Parent or legal guardian must provide written consent for patients \<18 years of age.
* Age 18-75 years.
* Recipient of simultaneous pancreas and kidney transplant
* Primary or secondary renal allograft: living or deceased

Exclusion Criteria:

* Patient has previously received or is receiving an organ transplant other than a pancreas-kidney.

Primary outcomes:
measure: Retrospective and prospective analysis of pancreas transplant recipients to determine frequency, and time course of autoantibody recurrence of disease. Prospective follow up to: monitor autoantibody levels, monitor and phenotype autoreactive T
timeFrame: up to 5 years
Secondary outcomes:
measure: Monitor autoantibody levels as well as phenotype autoreactive T cells in peripheral blood.
timeFrame: up to 15 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Miller School of Medicine Transplant Clinic
state: Florida
Study officials:
affiliation: University of Miami
name: George Burke, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vendrame F, Hopfner YY, Diamantopoulos S, Virdi SK, Allende G, Snowhite IV, Reijonen HK, Chen L, Ruiz P, Ciancio G, Hutton JC, Messinger S, Burke GW 3rd, Pugliese A. Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas-Kidney Transplants. Am J Transplant. 2016 Jan;16(1):235-45. doi: 10.1111/ajt.13426. Epub 2015 Aug 28.
citation: Burke GW 3rd, Vendrame F, Virdi SK, Ciancio G, Chen L, Ruiz P, Messinger S, Reijonen HK, Pugliese A. Lessons From Pancreas Transplantation in Type 1 Diabetes: Recurrence of Islet Autoimmunity. Curr Diab Rep. 2015 Dec;15(12):121. doi: 10.1007/s11892-015-0691-5.
citation: Pugliese A, Vendrame F, Reijonen H, Atkinson MA, Campbell-Thompson M, Burke GW. New insight on human type 1 diabetes biology: nPOD and nPOD-transplantation. Curr Diab Rep. 2014 Oct;14(10):530. doi: 10.1007/s11892-014-0530-0.
citation: Pugliese A, Yang M, Kusmarteva I, Heiple T, Vendrame F, Wasserfall C, Rowe P, Moraski JM, Ball S, Jebson L, Schatz DA, Gianani R, Burke GW, Nierras C, Staeva T, Kaddis JS, Campbell-Thompson M, Atkinson MA. The Juvenile Diabetes Research Foundation Network for Pancreatic Organ Donors with Diabetes (nPOD) Program: goals, operational model and emerging findings. Pediatr Diabetes. 2014 Feb;15(1):1-9. doi: 10.1111/pedi.12097. Epub 2013 Dec 10.
citation: Ciancio G, Sageshima J, Chen L, Gaynor JJ, Hanson L, Tueros L, Montenora-Velarde E, Gomez C, Kupin W, Guerra G, Mattiazzi A, Fornoni A, Pugliese A, Roth D, Wolf M, Burke GW 3rd. Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years. Am J Transplant. 2012 Dec;12(12):3363-76. doi: 10.1111/j.1600-6143.2012.04235.x. Epub 2012 Sep 4.