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The Norwegian Pancreas Transplantation (PTx) Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Oslo University Hospital
Sponsor:
Collaborator:
Aarhus University Hospital
Information provided by (Responsible Party):
Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT01957696
First received: September 30, 2013
Last updated: October 9, 2013
Last verified: October 2013
  Purpose

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


Condition Phase
Diabetes Mellitus
Pancreas Transplantation
Allograft Rejection
Surgical Complication Nec
Allograft Biopsies
Phase 4

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: A Prospective, Observational Study in Pancreatic Allograft Recipients: The Effect of Risk Factors, Immunosuppressive Level and the Benefits of Scheduled Biopsies - on Surgical Complications, Rejections and Graft Survival

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • Incidence of acute rejection episodes after pancreas- or pancreas- + kidney- transplantation [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

    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.


  • Surgical complications [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Compare the incidence of surgical complications, involving reoperations and reinterventions, between the prospective study cohort and retrospective control group.


Secondary Outcome Measures:
  • Graft survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Record kidney (and pancreas) graft survival (SPK) 12, 36 and 60 months post-Tx

  • Patient survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Compare patient survival at 12, 36 and 60 months post-Tx.

  • Non-surgical complications [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Compare the incidence of non-surgical complications; infections, cardial complications, pulmonary complications and neurological complications.


Other Outcome Measures:
  • Immunological analyses in blood samples [ Time Frame: 5 years ] [ Designated as safety issue: No ]

    Blood samples will be obtained at the time of transplantation and later scheduled time points:

    • Study of immune cell activation (CD25, FOXP3, CD4, CD3, CD8, CD45RO, perforin, granzyme A/B, etc) and cytokines (IL-2, TNF-a, IFN-g, IL-10, IL-12 etc).
    • Compare biomarkers in serum, indicative of acute rejection, by at least weekly blood sampling post-Tx (RNA microarray on a series of genes related to rejection, quantitative PCR on selected genes)
    • Study Pancreas Auto-antibodies

  • Immunological analyses in allograft biopsies [ Time Frame: 12 mts ] [ Designated as safety issue: No ]

    Scheduled biopsies will be taken at 3 wks, 6 wks and 12 mts post-Tx; as well as indication biopsies, simultaneously from these four transplant/organ sources: Pancreas-Tx (P); Kidney-Tx (K); Duodenal segment of pancreas-Tx (tD); Native Duodenum (nD; serves as control)

    • Immunohistochemistry on immunologic markers (CD25, FOXP3, CD4, CD3, CD8, CD45RO, perforin, granzyme A/B, etc)
    • DNA/RNA- analyses on immunologic markers; PCR, RNA microarray

  • Endoscopic mucosal imaging and ultrasound [ Time Frame: 12 mts ] [ Designated as safety issue: No ]
    • During upper endoscopy for scheduled biopsies (at 3 wks, 6 wks and 12 mts post-Tx), pictures of the transplant duodenal mucosa will be taken. The mucosal images will be rated regarding rubor, edema villous atrophy etc. and compared to biopsy rejection scores.
    • Endoscopic ultrasound (EUS) will be used during biopsying of the pancreas. EUS images will be sampled and stored, for comparative analysis. The EUS analysis will mainly involve circulatory parameters.

  • Donor and recipient baseline characteristics [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

    We will investigate relationships between the below mentioned donor/recipient characteristics and graft survival/surgical complications/non-surgical complications:

    • Donor age
    • Donor gender
    • Donor BMI
    • Recipient age
    • Recipient gender
    • Recipient BMI
    • Recipient PRA (Panel Reactive Antibody) status
    • Recipient comorbidity status; particularly cardiovascular status

  • Non-immunological rejection markers [ Time Frame: 12 mts ] [ Designated as safety issue: No ]

    The following analyses will be performed and correlated to rejection, functional parameters (glucose levels/need for insulin (P) and creatinine (K)), and graft survival. By daily blood samples during the first 10 days, 3 times a week until week 10, at 3 & 12 mts, and on indication.

    • Amylase (pancreas specific amylase)
    • Lipase
    • CRP
    • Amylase/Lipase/CRP combined parameter
    • C-peptide and C-peptide/Glucose/Creatinine-ratio (C-peptide : Glucose x Creatinine)
    • In addition, amylase in drainage fluid will be measured daily, until the drains are removed (usually at day 4-8 post-Tx).


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

Estimated Enrollment: 80
Study Start Date: September 2013
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01957696

Contacts
Contact: Ole M Øyen, MD, PhD +47 92264777 ole.oyen@ous-hf.no
Contact: Rune Horneland, MD +47 91177121 rune.horneland@ous-hf.no

Locations
Norway
Oslo University Hospital Recruiting
Oslo, Norway, 0027
Contact: Ole M Øyen, MD, PhD    +47 92264777    ole.oyen@ous-hf.no   
Contact: Rune Horneland, MD    +47 91177121    rune.horneland@ous-hf.no   
Principal Investigator: Ole M Øyen, MD, PhD         
Sponsors and Collaborators
Oslo University Hospital
Aarhus University Hospital
Investigators
Principal Investigator: Ole M Øyen, MD, PhD Oslo University Hospital
  More Information

Additional Information:
Publications:

Responsible Party: Oslo University Hospital
ClinicalTrials.gov Identifier: NCT01957696     History of Changes
Other Study ID Numbers: OUS-PTx-01
Study First Received: September 30, 2013
Last Updated: October 9, 2013
Health Authority: Norway: Regional Ethics Commitee

Keywords provided by Oslo University Hospital:
Diabetes mellitus
Pancreas transplantation
Rejection
Surgical complications
Allograft biopsies
Immunological analyses
Pancreas graft survival

Additional relevant MeSH terms:
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatin
Pancrelipase
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014