The Norwegian Pancreas Transplantation (PTx) Study

NCT01957696 | Enrolling By Invitation

• 1 other identifier: OUS-PTx-01
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Several studies have shown acceptable results after Pancreas Transplantation (PTx) by substituting ATG with basiliximab, which is considered to convey a considerably lower number of adverse events. However, our experiences with ATG in PTx (introduced in 2004) are good, and our presumably gentle way of administrating the drug - directed by T-cell counts - is in fact unique. The potential advantages of reducing the overall corticosteroid (CS) load is obvious, as CS is a well-known pro-diabetic agent and causes severe long term adverse effects. On this background, the investigators have very recently reduced our CS dosing (in the routine protocol) to a level corresponding to our Kidney Tx protocol (valid since 2009). Thus, the investigators intend to prospectively investigate a single PTx cohort with the reduced CS immunosuppressive protocol by an observational study design, and compare with previous (historical) cohorts, who have received high dose CS. Study hypotheses: i) Low-dose CS is as effective as high-dose corticosteroids with regards to efficacy/rejections; ii) The rate of surgical and infectious complications will be similar or lower in the low-dose group; iii) PTx rejection surveillance by DD (duodenoduodeno-stomy) and EUSPB (Endoscopic Ultra-Sound guided Pancreas Biopsies) is superior to traditional rejection surveillance; iv) Patient and graft survival is similar in the two groups

Conditions

Diabetes Mellitus; Pancreas Transplantation; Allograft Rejection; Surgical Complication Nec; Allograft Biopsies

Keywords

Diabetes mellitus; Pancreas transplantation; Rejection; Surgical complications; Allograft biopsies; Immunological analyses; Pancreas graft survival

Outcome Measures

Primary Outcomes (2)

• Incidence of acute rejection episodes after pancreas- or pancreas- + kidney- transplantation

  Compare the incidence of acute rejection episodes at 6, 12, 36 and 60 months after pancreas transplantation, between our single prospective cohort with lower CS vs a historic, retrospective control group (PTx performed during 2011-2013). The incidence of rejection is defined as the fraction of patients in which rejections episodes (one or more) have been proven by biopsies. For SPK rejection in either organ, pancreas or kidney, counts. Furthermore, we will compare the number and severity of rejection episodes in the pancreas allograft to the ones occurring in the kidney allograft (SPK), and the ones diagnosed by the duodenal segment biopsies.

  5 years

• Surgical complications

  Compare the incidence of surgical complications, involving reoperations and reinterventions, between the prospective study cohort and retrospective control group.

  5 years

Secondary Outcomes (3)

• Graft survival

  5 years

• Patient survival

  5 years

• Non-surgical complications

  5 years

Other Outcomes (8)

• Immunological analyses in blood samples

  5 years

• Immunological analyses in allograft biopsies

  12 mts

• Endoscopic mucosal imaging and ultrasound (EUS) w/ biopsies of the pancreas graft and duodenal segment.

  12 mts

Study Arms (1)

Pancreas-Tx recipients; single cohort

This is a prospective, single cohort observational study, aimed at using a historical control group as comparison. It will be conducted at our single, national centre for organ transplantation in Oslo. All pancreas recipients \> 18 years of age, who fulfill the inclusion criteria, will prior to transplantation be asked for inclusion.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will be conducted at our single, national centre for organ transplantation in Oslo. All consecutive Pancreas-Tx recipients during 2-3 years are planned to be enrolled, with an intented number of 60-80 patients. The study will continue until all patients have completed a minimum of 60 months of follow-up or have discontinued participation in the study.

You may qualify if:

• Age ≥18 years
• Patients who receive a primary or secondary pancreas transplant, with or without a simultaneous kidney transplant (SPK).
• Women who are of childbearing potential must have a negative serum pregnancy test at baseline.
• Operability has to be ascertained by preoperative examination, performed by nephrologist, transplant surgeon and anaesthesiologist.
• Signed and dated informed consent form.

You may not qualify if:

• Evidence of systemic infection
• Presence of unstable cardiovascular disease.
• Malignancy \< 5 years prior to entry into the trial (with the exception of adequately treated basal cell or squamous cell carcinomas of the skin).
• Panel-reactive antibodies (PRA) \> 20% or the presence of donor-specific antigens (DSA).
• Any positive test for HBV, HBC or HIV.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Oslo University Hospital

Oslo, 0027, Norway

Location

Related Publications (22)

• Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery. 1967 Jun;61(6):827-37. No abstract available.

  PMID: 5338113 BACKGROUND

• Gruessner AC. 2011 update on pancreas transplantation: comprehensive trend analysis of 25,000 cases followed up over the course of twenty-four years at the International Pancreas Transplant Registry (IPTR). Rev Diabet Stud. 2011 Spring;8(1):6-16. doi: 10.1900/RDS.2011.8.6. Epub 2011 May 10.

  PMID: 21720668 BACKGROUND

• Sutherland DE, Gruessner RW, Dunn DL, Matas AJ, Humar A, Kandaswamy R, Mauer SM, Kennedy WR, Goetz FC, Robertson RP, Gruessner AC, Najarian JS. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001 Apr;233(4):463-501. doi: 10.1097/00000658-200104000-00003.

  PMID: 11303130 BACKGROUND

• Sollinger HW, Odorico JS, Becker YT, D'Alessandro AM, Pirsch JD. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Ann Surg. 2009 Oct;250(4):618-30. doi: 10.1097/SLA.0b013e3181b76d2b.

  PMID: 19730242 BACKGROUND

• Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999 Dec 2;341(23):1725-30. doi: 10.1056/NEJM199912023412303.

  PMID: 10580071 BACKGROUND

• Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, Klarenbach S, Gill J. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011 Oct;11(10):2093-109. doi: 10.1111/j.1600-6143.2011.03686.x. Epub 2011 Aug 30.

  PMID: 21883901 BACKGROUND

• Brekke IB. Indications and results of pancreatic transplantation: the Oslo experience 1983-1990. Diabetologia. 1991 Aug;34 Suppl 1:S18-20. doi: 10.1007/BF00587612.

  PMID: 1936687 BACKGROUND

• Bentdal OH, Fauchald P, Brekke IB, Holdaas H, Hartmann A. Rehabilitation and quality of life in diabetic patients after successful pancreas-kidney transplantation. Diabetologia. 1991 Aug;34 Suppl 1:S158-9. doi: 10.1007/BF00587645.

  PMID: 1936685 BACKGROUND

• Brekke IB. Duct-drained versus duct-occluded pancreatic grafts: a personal view. Transpl Int. 1993 Mar;6(2):116-20. doi: 10.1007/BF00336656. No abstract available.

  PMID: 8447925 BACKGROUND

• Brekke IB, Bentdal O, Pfeffer P, Lien B, Sodal G, Holdaas H, Fauchald P, Jervell J. [Pancreas transplantation. A 10-year material]. Tidsskr Nor Laegeforen. 1995 Feb 28;115(6):703-5. Norwegian.

  PMID: 7900130 BACKGROUND

• Brekke IB. [Pancreas transplantation--a review]. Tidsskr Nor Laegeforen. 1999 Sep 20;119(22):3305-9. Norwegian.

  PMID: 10533414 BACKGROUND

• Lindahl JP, Hartmann A, Horneland R, Holdaas H, Reisaeter AV, Midtvedt K, Leivestad T, Oyen O, Jenssen T. Improved patient survival with simultaneous pancreas and kidney transplantation in recipients with diabetic end-stage renal disease. Diabetologia. 2013 Jun;56(6):1364-71. doi: 10.1007/s00125-013-2888-y. Epub 2013 Apr 3.

  PMID: 23549518 BACKGROUND

• Margreiter C, Aigner F, Resch T, Berenji AK, Oberhuber R, Sucher R, Profanter C, Veits L, Ollinger R, Margreiter R, Pratschke J, Mark W. Enteroscopic biopsies in the management of pancreas transplants: a proof of concept study for a novel monitoring tool. Transplantation. 2012 Jan 27;93(2):207-13. doi: 10.1097/TP.0b013e31823cf953.

  PMID: 22134369 BACKGROUND

• Rogers J, Farney AC, Al-Geizawi S, Iskandar SS, Doares W, Gautreaux MD, Hart L, Kaczmorski S, Reeves-Daniel A, Winfrey S, Ghanta M, Adams PL, Stratta RJ. Pancreas transplantation: lessons learned from a decade of experience at Wake Forest Baptist Medical Center. Rev Diabet Stud. 2011 Spring;8(1):17-27. doi: 10.1900/RDS.2011.8.17. Epub 2011 May 10.

  PMID: 21720669 BACKGROUND

• Meier-Kriesche HU, Li S, Gruessner RW, Fung JJ, Bustami RT, Barr ML, Leichtman AB. Immunosuppression: evolution in practice and trends, 1994-2004. Am J Transplant. 2006;6(5 Pt 2):1111-31. doi: 10.1111/j.1600-6143.2006.01270.x.

  PMID: 16613591 BACKGROUND

• Schulz T, Flecken M, Kapischke M, Busing M. Single-shot antithymocyte globuline and daclizumab induction in simultaneous pancreas and kidney transplant recipient: three-year results. Transplant Proc. 2005 May;37(4):1818-20. doi: 10.1016/j.transproceed.2005.02.087.

  PMID: 15919476 BACKGROUND

• Boggi U, Vistoli F, Amorese G, Giannarelli R, Coppelli A, Mariotti R, Rondinini L, Barsotti M, Piaggesi A, Tedeschi A, Signori S, De Lio N, Occhipinti M, Mangione E, Cantarovich D, Del Prato S, Mosca F, Marchetti P. Results of pancreas transplantation alone with special attention to native kidney function and proteinuria in type 1 diabetes patients. Rev Diabet Stud. 2011 Summer;8(2):259-67. doi: 10.1900/RDS.2011.8.259. Epub 2011 Aug 10.

  PMID: 22189549 BACKGROUND

• Ollinger R, Margreiter C, Bosmuller C, Weissenbacher A, Frank F, Schneeberger S, Mark W, Margreiter R, Pratschke J. Evolution of pancreas transplantation: long-term results and perspectives from a high-volume center. Ann Surg. 2012 Nov;256(5):780-6; discussion 786-7. doi: 10.1097/SLA.0b013e31827381a8.

  PMID: 23095622 BACKGROUND

• Wu T, Abu-Elmagd K, Bond G, Nalesnik MA, Randhawa P, Demetris AJ. A schema for histologic grading of small intestine allograft acute rejection. Transplantation. 2003 Apr 27;75(8):1241-8. doi: 10.1097/01.TP.0000062840.49159.2F.

  PMID: 12717210 BACKGROUND

• Li L, Khatri P, Sigdel TK, Tran T, Ying L, Vitalone MJ, Chen A, Hsieh S, Dai H, Zhang M, Naesens M, Zarkhin V, Sansanwal P, Chen R, Mindrinos M, Xiao W, Benfield M, Ettenger RB, Dharnidharka V, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Davis R, Butte AJ, Salvatierra O, Sarwal MM. A peripheral blood diagnostic test for acute rejection in renal transplantation. Am J Transplant. 2012 Oct;12(10):2710-8. doi: 10.1111/j.1600-6143.2012.04253.x.

  PMID: 23009139 BACKGROUND

• Allison SJ. Transplantation: Biomarkers in peripheral blood detect acute rejection. Nat Rev Nephrol. 2012 Dec;8(12):681. doi: 10.1038/nrneph.2012.227. Epub 2012 Oct 16. No abstract available.

  PMID: 23070573 BACKGROUND

• Rydenfelt K, Kjosen G, Horneland R, Ludviksen JK, Jenssen TG, Line PD, Tonnessen TI, Mollnes TE, Haugaa H, Pischke SE. Thromboinflammatory response is increased in pancreas transplant alone versus simultaneous pancreas-kidney transplantation and early pancreas graft thrombosis is associated with complement activation. Front Immunol. 2023 Mar 29;14:1044444. doi: 10.3389/fimmu.2023.1044444. eCollection 2023.

  PMID: 37063904 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be obtained at the time of Tx and later scheduled time points to: * Study of immune cell activation (CD25, FOXP3, CD4, CD3, CD8, CD45RO, perforin, granzyme A/B, etc) and cytokines (IL-2, IL-12 etc) * Compare biomarkers in serum, indicative of acute rejection; RNA microarray on a series of genes related to rejection, quantitative PCR on selected genes) Scheduled biopsies will be taken according to our present routine protocol at 3 wks, 6 wks and 12 mts post-Tx, as well as indication biopsies; simultaneosly from these four transplant/organ sources: Pancreas-Tx (P); Kidney-Tx (K); Duodenal segment of pancreas-Tx (tD; Native Duodenum (control) Histological and molecular evaluations will involve: * Rejection histology scores * Immunoshistochemistry on immunologic markers (CD25, FOXP3, CD4, CD3, CD8, CD45RO, perforin, granzyme A/B, etc) * DNA/RNA analyses on immunologic markers: PCR, RNA microarray

MeSH Terms

Conditions

Diabetes Mellitus; Rejection, Psychology

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Social Behavior; Behavior

Study Officials

• Ole M Øyen, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Håkon Haugaa, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 30, 2013
• First Posted: October 8, 2013
• Study Start: September 1, 2013
• Primary Completion: April 29, 2019
• Study Completion (Estimated): October 1, 2028
• Last Updated: May 10, 2019

Record last verified: 2019-05

Locations

NO (1)