Islet Autotransplantation in Patients at Very High-risk Pancreatic Anastomosis (PAN-IT)

This study is currently recruiting participants.
Verified October 2012 by Ospedale San Raffaele
Sponsor:
Collaborator:
Ministry of education, university and research, Italy
Information provided by (Responsible Party):
Piemonti Lorenzo, Scientific Institute San Raffaele
ClinicalTrials.gov Identifier:
NCT01346098
First received: April 29, 2011
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

The goal of the proposal is to demonstrate that, in patients with disease of the pancreatic head with very high-risk of complications of pancreatojejunal reconstruction (soft pancreas and pancreatic duct diameter <3 mm), total pancreatectomy with islet autotransplantation (IAT) is associated with a lower morbidity (in terms of surgical or medical complications) and mortality compared with pancreaticoduodenectomy and pancreatojejunal anastomosis.


Condition Intervention Phase
Postpancreatectomy Hyperglycemia
Procedure: Pancreaticoduodenectomy with pancreatic anastomosis
Procedure: Total pancreatectomy with islet autotransplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Total Pancreatectomy With Islet Autotransplantation as a Superior Alternative to Pancreatoduodenectomy in Patients at Very High-risk of Complications of the Pancreatic Anastomosis: a Single-center Prospective Randomised Clinical Trial

Resource links provided by NLM:


Further study details as provided by Ospedale San Raffaele:

Primary Outcome Measures:
  • incidence of complications after pancreatic surgery [ Time Frame: 90 days from discharge ] [ Designated as safety issue: Yes ]
    Complications will be defined and graded according to the Novel Grading System classification ( DeOliveira et al 2006). A special emphasis is given to life-threatening and permanently disabling complications.


Secondary Outcome Measures:
  • Incidence of each individual postoperative complication [ Time Frame: 90 days from discharge ] [ Designated as safety issue: Yes ]
    1. death
    2. pancreatic fistula defined according to the International Study Group on Pancreatic Fistula (Bassi C et al 2005)
    3. delayed gastric emptying (DGE) defined according to the International Study Group on Pancreatic Fistula (Wente et al 2007)
    4. intra-abdominal complications
    5. medical complications

  • Incidence of endocrine and exocrine pancreatic insufficiency [ Time Frame: 12 months after surgery. ] [ Designated as safety issue: Yes ]

    We will assess endocrine pancreatic function by measuring fasting plasma glucose and HbA1c in all patients.

    Clinical hallmarks of pancreatic exocrine insufficiency include symptoms of fat malabsorption, such as steatorrhea, weight loss and abdominal pain. Frequency of bowel movements and characteristics of stools will be serially recorded. Fat-soluble vitamins such as A, D, E and K will be measured 12 month after the hospital discharge after the index surgery. Oral pancreatic enzyme supplementation will be prescribed according to the severity of clinical steatorrhea and weight loss.



Estimated Enrollment: 60
Study Start Date: July 2010
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GROUP B
At the time of surgery the surgeon will directly assess pancreatic consistency and the pancreatic duct size. In the presence of a soft pancreas and a small duct (diameter <3 mm), the patient will be randomly assigned to receive either a pancreaticoduodenectomy with pancreatic anastomosis (group A) or a total pancreatectomy with IAT (group B).
Procedure: Total pancreatectomy with islet autotransplantation
If the patient will be assigned to this group, the surgeon will complete the pancreatectomy preserving the spleen. The body and tail of the pancreas will be sent to the islet isolation facility. Islets will be isolated and purified according to the automated method described by Ricordi. The resulting islet tissue will be suspended in a cold isotonic saline solution and infused into the portal vein during the next 24h.
Active Comparator: GROUP A Procedure: Pancreaticoduodenectomy with pancreatic anastomosis
Standard lymphadenectomy, end-to-side two-layer pancreaticojejunostomy and duodenojejunostomy will be performed. If the pylorus is preserved, so will be the right gastric artery, unless the artery is damaged or hindering adequate gastric mobilization. No prokinetic agent will be administered routinely, but IV metoclopramide will given on demand (10 mg , three times daily). Prophylaxis will consist of octreotide (0,1 mg three times daily from day 0 to 7), low molecular weight heparin and a single dose of antibiotic (cefazolin 2 g). Early postoperative analgesia will be achieved by epidural or, when contraindicated, patient-controlled analgesia

Detailed Description:

Complications of the pancreatic anastomosis still represents a significant risk for death after the resection of the pancreatic head. In an effort to decrease morbidity and mortality, the referral of patients who need a pancreaticoduodenectomy to institutions (and surgeons) performing a high volume of this surgical procedure has been championed. Nonetheless, the role of prophylactic medications and the best surgical technique(s) for the removal of the pancreatic head are still debated. However, very few prospective randomized clinical trials have been conducted to compare different surgical techniques.

Our study will address for the first time the role for preemptive total pancreatectomy and IAT in selected patients undergoing pancreaticoduodenectomy that are considered high risk for pancreaticojejunostomy disruption (eg, small pancreatic duct, soft pancreas). The information expected is the identification of total pancreatectomy and the IAT as the standard treatment in a subgroup of patient with pathologies of the pancreatic head at high risk for leakage of pancreatic anastomosis. Ultimately this project will lead to reserve more innovative cell therapy for patients with the highest risk of anastomosis failure reducing pancreatojejunal reconstruction related morbidity and mortality

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients >18 years of age
  • Ability to provide written informed consent
  • Mentally stable and able to comply with the procedures of the study protocol
  • Fasting glycaemia <126 mg/dl without glucose-lowering medications.

Exclusion Criteria:

  • Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial
  • Diagnosis of intraductal papillary mucinous cancer, unless the absence of multifocal lesion is demonstrated by endoscopic US
  • Presence of multifocal or residual disease at the pancreatic margin.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01346098

Contacts
Contact: Lorenzo Piemonti, MD 390226432706 piemonti.lorenzo@hsr.it
Contact: Gianpaolo Balzano, MD 390226432664 balzano.gianpaolo@hsr.it

Locations
Italy
IRCCS San Raffaele Recruiting
Milan, Italy, 20132
Contact: Gianpaolo Balzano, MD    390226432664    gianpaolo.balzano@hsr.it   
Contact: Lorenzo Piemonti, MD    390226432706    lorenzo.piemonti@hsr.it   
Sponsors and Collaborators
Ospedale San Raffaele
Ministry of education, university and research, Italy
Investigators
Principal Investigator: Lorenzo Piemonti, MD Fondazione Centro San Raffaele del Monte Tabor
Study Director: Gianpaolo Balzano, MD Fondazione Centro San Raffaele del Monte Tabor
  More Information

No publications provided

Responsible Party: Piemonti Lorenzo, Director Islet Transplantation Program, Scientific Institute San Raffaele
ClinicalTrials.gov Identifier: NCT01346098     History of Changes
Other Study ID Numbers: PAN-IT
Study First Received: April 29, 2011
Last Updated: October 3, 2012
Health Authority: Italy: National Institute of Health

Keywords provided by Ospedale San Raffaele:
diabetes
islet transplantation
pancreas
pancreatectomy

Additional relevant MeSH terms:
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on April 17, 2014