Two-Layer Method Preservation and Resuscitation of the Cadaveric Pancreas Before Transplantation

The purpose of this project is to compare the effect of oxygenated preservation of the pancreas before transplantation using the "Two-Layer Method" (TLM) against outcomes previously experienced with organs preserved using only standard University of Wisconsin (UW) storage solution. It is our hypothesis that TLM preservation will reduce the frequency and severity of complications of pancreas transplantation, increase the number of organs acceptable for transplantation, and spare individual patients and their families suffering and hardship.

Study Overview

• Status: Terminated
• Conditions: Graft Pancreatitis
• Intervention / Treatment: Drug: Two-Layer Method pancreas preservation system drug; Device: Two-Layer Method pancreas preservation system device

Detailed Description

Two-Layer Method (TLM) preservation consists of a storage chamber containing a layer of highly oxygenated, water-immiscible liquid perfluorocarbon (perfluorodecalin, C10F18) surmounted by a layer of conventional UW (or similar) organ preservation solution. The perfluorocarbon is sufficiently dense (~2 g/ml) that the pancreas floats on top of it, in contact with both layers. The perfluorocarbon combines low toxicity with an oxygen content 75 times greater than the UW solution used in standard pancreas storage. When preserved under these conditions, the pancreas absorbs oxygen by diffusion and steadily consumes it, supporting sufficient aerobic metabolism to maintain tissue ATP concentrations at near-physiologic levels and prevent, or even reverse, pancreas anoxic injury. In animal models of pancreas ischemic and storage injury, TLM preservation has been strikingly successful at improving the outcome of both islet isolation and pancreas transplantation.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • The Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Listed for pancreas transplantation at the University of Nebraska Medical Center

Exclusion Criteria:

• Ineligibility for medical/surgical/psychosocial reasons for listing for pancreas transplantation at the University of Nebraska Medical Center.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pancreas Preservation; The pancreas will be preserved before transplantation in an oxygenated system containing highly oxygenated liquid perfluorocarbon (perfluorodecalin, C10F18. The perfluorocarbon combines low toxicity with a capacity to dissolve 75 times more oxygen than the UW solution used in standard pancreas storage. When preserved under these conditions, the pancreas absorbs oxygen by diffusion and steadily consumes it, supporting sufficient aerobic metabolism to maintain tissue ATP concentrations at near-physiologic levels and prevent, or even reverse, pancreas anoxic injury.

Drug: Two-Layer Method pancreas preservation system drug; Preserving the pancreas before transplantation in an oxygenated system containing highly oxygenated liquid perfluorocarbon (perfluorodecalin, C10F18. The perfluorocarbon combines low toxicity with a capacity to dissolve 75 times more oxygen than the UW solution used in standard pancreas storage. When preserved under these conditions, the pancreas absorbs oxygen by diffusion and steadily consumes it, supporting sufficient aerobic metabolism to maintain tissue ATP concentrations at near-physiologic levels and prevent, or even reverse, pancreas anoxic injury.; Other Names: pancreas preservation; Device: Two-Layer Method pancreas preservation system device; Preserving the pancreas before transplantation in an oxygenated system containing highly oxygenated liquid perfluorocarbon (perfluorodecalin, C10F18. The perfluorocarbon combines low toxicity with a capacity to dissolve 75 times more oxygen than the UW solution used in standard pancreas storage. When preserved under these conditions, the pancreas absorbs oxygen by diffusion and steadily consumes it, supporting sufficient aerobic metabolism to maintain tissue ATP concentrations at near-physiologic levels and prevent, or even reverse, pancreas anoxic injury.; Other Names: pancreas preservation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-transplantation adverse event frequency	Post-transplantation adverse event frequency (graft thrombosis, hemorrhage, peri-pancreatic abscess, re-laparotomy, cadaver duodenum leak, pseudo-aneurysm formation, rejection, graft failure, patient death)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standard post-transplantation morbidity endpoints	Standard post-transplantation morbidity endpoints including fungal, bacterial, and viral infections, and incidence and rate of stroke and heart attack. Length of hospital stay and re-admission and re-operation rates will also be monitored.	1 year

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: R Brian Stevens, MD, PhD, University of Nebraska

Publications and helpful links

General Publications

• Matsumoto S, Kandaswamy R, Sutherland DE, Hassoun AA, Hiraoka K, Sageshima J, Shibata S, Tanioka Y, Kuroda Y. Clinical application of the two-layer (University of Wisconsin solution/perfluorochemical plus O2) method of pancreas preservation before transplantation. Transplantation. 2000 Sep 15;70(5):771-4. doi: 10.1097/00007890-200009150-00010.
• Hiraoka K, Kuroda Y, Suzuki Y, Fujino Y, Tanioka Y, Matsumoto S, Sakai T, Kandaswamy R, Sutherland DE. Outcomes in clinical pancreas transplantation with the two-layer cold storage method versus simple storage in University of Wisconsin solution. Transplant Proc. 2002 Nov;34(7):2688-9. doi: 10.1016/s0041-1345(02)03376-6. No abstract available.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: December 17, 2007
• First Submitted That Met QC Criteria: December 27, 2007
• First Posted (Estimated): January 14, 2008

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: organ preservation; Pancreas transplantation; graft pancreatitis; Two-layer method
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Graft; Gastrointestinal Agents; Pancrelipase; Pancreatin
• Other Study ID Numbers: 0047-07-FB; IDE G060082

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes