Diabetes Mellitus Clinical Trial
— PTxOfficial 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
Verified date | May 2019 |
Source | Oslo University Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational [Patient Registry] |
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
Status | Enrolling by invitation |
Enrollment | 80 |
Est. completion date | October 2028 |
Est. primary completion date | April 29, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
Norway | Oslo University Hospital | Oslo |
Lead Sponsor | Collaborator |
---|---|
Oslo University Hospital | Aarhus University Hospital |
Norway,
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. — View Citation
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Brekke IB, Bentdal O, Pfeffer P, Lien B, Sødal G, Holdaas H, Fauchald P, Jervell J. [Pancreas transplantation. A 10-year material]. Tidsskr Nor Laegeforen. 1995 Feb 28;115(6):703-5. Norwegian. — View Citation
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Lindahl JP, Hartmann A, Horneland R, Holdaas H, Reisæter 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. — View Citation
Margreiter C, Aigner F, Resch T, Berenji AK, Oberhuber R, Sucher R, Profanter C, Veits L, Öllinger 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. — View Citation
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* Note: There are 21 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Immunological analyses in blood samples | 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 |
5 years | |
Other | Immunological analyses in allograft biopsies | 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 |
12 mts | |
Other | Endoscopic mucosal imaging and ultrasound (EUS) w/ biopsies of the pancreas graft and duodenal segment. | During upper endoscopy for scheduled biopsies of the pancreas and duodenal segment (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. |
12 mts | |
Other | Donor and recipient baseline characteristics | 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 |
5 years | |
Other | Non-immunological rejection markers | 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). |
12 mts | |
Other | Explore if potentially graft devastating complications in pancreas transplants can be detected with the microdialysis method. [Amendment 1; Approved by Regional Ethics Commitee] | At the end of surgery one catheter will be positioned ventral and one dorsal on the outside of the pancreas transplant. Each catheter will be perfused with 6 % hydroxyethyl starch at a rate of 1 µL/minute. Postoperatively, the microdialysis samples will be analyzed at the bedside for glycerol, glucose, lactate, and pyruvate using a microdialysis analyzer. Samples from both catheters will be analyzed hourly the first 24 hours and thereafter every two hours during daytime and every three hours during the night (00, 03, and 06). The catheters will be left in situ for as long as they are able to sample appropriately, or until the patient is dismissed. All microdialysis samples will be frozen at -80°C after they have been analyzed for mediators of intermediate metabolism. We will also collect EDTA plasma daily. After study completion, the microdialysis and plasma samples will be analyzed en bloc for an array of inflammatory mediators. | 4 weeks | |
Other | Scheduled Ultrasound and CT examinations at postop. day 5-7 [Amendment 3; Approved by Regional Ethics Commitee] | Ultrasound and CT examinations will be performed at postop. day 5-7 in order to: Detect thrombotic events in the PTx and compare the results with the metabolic patterns obtained from the microdialysis cathethers. Control the position of the microdialysis catheters Detect other pathology; fluid accumulations, abscesses etc. Compare the results/efficacy/sensistivity between Ultrasound and CT. |
1 week | |
Other | Scheduled, conventional, percutaneous, ultrasound-guided pancreas graft biopsies at 6 weeks and 12 months post-Tx [Amendment 2; Approved by Regional Ethics Commitee] | We also want to take conventional percutaneous, ultrasound-guided pancreas biopsies at 6 weeks and 12 months post-Tx - in order to compare the yield (and complications) by EUS (Cfr. Outcome 8) vs percutaneous P biopsies. | 12 mts | |
Primary | 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 | |
Primary | Surgical complications | Compare the incidence of surgical complications, involving reoperations and reinterventions, between the prospective study cohort and retrospective control group. | 5 years | |
Secondary | Graft survival | Record kidney (and pancreas) graft survival (SPK) 12, 36 and 60 months post-Tx | 5 years | |
Secondary | Patient survival | Compare patient survival at 12, 36 and 60 months post-Tx. | 5 years | |
Secondary | Non-surgical complications | Compare the incidence of non-surgical complications; infections, cardial complications, pulmonary complications and neurological complications. | 5 years |
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