Desensitization for Highly Sensitized Recipients of Pancreas Transplantation

This is an observational study for patients with type 1 diabetes, whom are already scheduled to have desensitization treatment to help increase the chance of receiving a pancreas transplant.The study staff will be looking at medical records in order to collect past, present and future information for each subject's medical condition and/or transplant. There are no additional study tests, procedures or devices needed for our analysis.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes; Desensitization; Rejection of Pancreas Transplant

Detailed Description

Please note that this study is observational. The treatment of each patient will be at the discretion of the care physician. The study investigators will ONLY be performing data collection and analysis.

Post transplant all patients will receive one additional cycle of plasma exchange with a moderate dose of Intravenous Immunoglobulin (IVIg) (0.4 mg/Kg). Antibody titers will be monitoring prior to plasma exchange and immediately following the treatment. At this point, since donor antigens are known, only antibodies to these antigens will be tested to minimize cost. We anticipate that in some patients, especially if the original titer of donor-specific antibody (DSA) was high (> 1:128), a rise in DSA will be observed following transplant. If indeed DSA will be present, additional monitoring will be initiated and the patient will be treated further with plasma exchange/IVIg cycles, with antibody monitoring before and immediately after each cycle. If no DSA are detected, patients will be monitoring on a every other day schedule for the first week; weekly for the next 3 weeks and monthly up to 6 months post transplant. Additional testing will be performed in the event of any clinical evidence of graft dysfunction, or following sever infection events.

Patient will be followed to 12 month post transplant or until one of the end points is reached:

1. pancreas graft failure: defined by return of hyperglycemia and resume of insulin therapy;
2. patient death due to all causes with functioning graft

• Study Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of type 1 diabetes who are highly sensitized (defined as having panel reactive antibody (PRA) level >50%) who underwent successful desensitization treatment followed by a deceased donor pancreas transplantation at NMH .

Description

Inclusion Criteria:

• Pancreas transplant recipients with elevated panel reactive antibody levels of >50% and who have received desensitization treatment and subsequently receive their transplantation at Northwestern Memorial Hospital (NMH).

Exclusion Criteria:

• No Exclusion criteria exist.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success of surgical engraftment.	This is measured by standard blood flow perfusion scan. Adequate blood flow is demonstrated by appropriate radioactive tracer uptake by the pancreas allograft. Lack of blood flow will prompt immediate surgical intervention.	Post-operative day 1
Track the improvement of glycemic control.	Standard of care laboratory values measured routinely include: fasting and post-prandial glucose determination, serum C-peptide levels, improvement of Hemoglobin (A1C) levels post-transplant.	Standard-of-care labs throughout duration of study
Rejection free graft survival.	Serum amylase & lipase measured. Rising levels/aberrant glycemic control may indicate allograft rejection. Treatment - pancreas allograft rejection: 1) diagnosed by pancreas allograft biopsy; 2) if rejection, staining for C4d, repeat to DSA to determine rejection (acute antibody meditated humoral vs. acute cellular); 3) acute humoral rejection treated w/plasma exchange, then by Intravenous Immunoglobulin (IVIg) (0.5 gm/kg) every other day, daily polyclonal anti-thymocyte globulin (ATG) at 1.25 mg/kg. Treatment duration based on clinical response. Baseline immunosuppressive medications maintained during treatment.	12 Month follow-up from baseline
Patient and graft survival.	Patient and graft survival will be calculated at this time.	At 12 Month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tracking infection risks	Screening for viral infections will be performed according to standard of care protocol. Asymptomatic or symptomatic Cytomegalovirus (CMV) viremia will be treated in consultation with Transplant Infectious Diseases Services. Testing for bacterial and fungal infections will be guided by clinical suspicion. Active infection will again be treated in consultation with the Transplant Infectious Diseases Service.	Standard of care benchmarks through 12 months
Bleeding complications	Though increased risks for bleeding have been associated with repeated plasma exchanges that deplete clotting factors, review to evaluate whether the limited number of plasma exchanges used in the standard of care protocols will show a minimal increase of risks for bleeding. At 12 Month follow-up time points, the number of bleeding episodes, their temporal relation to plasma exchange, and frequency of requirement for factor replacement will be analyzed.	At 12 Months follow-up time points
Reversal or halting of diabetic complications	For diabetic nephropathy, serum creatinine levels and urine microalbuminuria will be measured. the use of ACE inhibitors, angiotensin receptor blocker, or aldosterone receptor blocker will be noted. For diabetic retinopathy, patients will be referred to an ophthalmologist at the 12 and 24 Months time points to measure diabetic retinal changes based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system.	0, 6, 12, 18, 24 Months

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Xunrong Luo, MD, PhD, Northwestern University

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: March 19, 2009
• First Posted (Estimate): March 23, 2009

Study Record Updates

• Last Update Posted (Estimate): March 13, 2014
• Last Update Submitted That Met QC Criteria: March 11, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: STU 14940; CNV0058087 (Other Identifier: Office for Sponsored Research, Northwestern University)