Aralast NP in Islet Transplant

Type 1 Diabetes Mellitus Clinical Trial

Official title: Improving Single Donor Success Rate in Clinical Islet Transplantation Using Alpha-1 Antitrypsin (Aralast NP)

Status Completed

Clinical Trial Summary

Islet transplantation is a relatively new procedure used in people with difficult to control Type 1 diabetes. Insulin producing cells (islets) are isolated from a pancreas donated by the next of kin of a person who is brain dead. After the cells are prepared, the islets are transplanted into the recipient's liver and produce insulin. Patients who receive an islet transplant take medication that suppresses their immune system and prevent rejection of the islet tissue.

The investigators have also learned that there is general inflammation at the time of the transplant that is not fully controlled with our standard medications. The investigators believe this inflammation may cause some islet cell death around the time of transplant. Due to this islet death around the time of transplant, most recipients need 2 or 3 separate transplant procedures.

The investigators are studying the use of Alpha-1 Antitrypsin (AAT) in islet transplant to decrease the amount of cell death caused by general inflammation. In this study, the investigators hope to decrease the need for more than one transplant procedure by controlling inflammation, before and after transplant, with Alpha-1 Antitrypsin (Aralast NP).

Alpha-1 Antitrypsin is a protein made in healthy humans that helps to prevent tissue damage during times of inflammation. Alpha-1 Antitrypsin is obtained from healthy plasma donors. There have been studies in Islet Transplant in monkeys using this medication and it has shown to protect the islets from inflammation.

This study involves using Alpha-1 Antitrypsin in addition to our current Standard of Care medications used in Islet Transplant.

Clinical Trial Description

METHODS & PROCEDURES:

This clinical trial will be a non-randomized, open-label, single arm, prospective trial to asses the efficacy of AAT in preventing non-immunologic loss of transplanted islet mass in a single-donor islet transplant. Enrolled patients (n=12) will participate in the study for 1 year, with outcomes assessed during islet isolation, 90 days post-transplant and at 1 year post-transplant.

The current Standard of Care treatment for Islet Transplant includes induction (Alemtuzumab/Basiliximab) and long-term immunosuppression (Prograf/Cellcept). The engraftment regimen includes anti-inflammatory medications (Etanercept/Anakinra) and intravenous insulin and heparin. We will utilize the current Islet Standard of Care Protocol. The only additional intervention used in this pilot trial is the addition of the investigational agent, alpha-1-antitrypsin to islet processing, culture, and patient treatment pre- and post-transplant.

Islet Dosage and Culture

Islets will be treated with AAT (to a final dilution of 0.5mg/mL) throughout the isolation and culture process. Islet treatment will include:

• Flushing through the superior mesenteric artery and splenic artery (final dilution 0.5mg/mL)

• Culturing with AAT (final dilution 0.5mg/mL)

Participant Dosing

Subjects undergoing intraportal clinical islet transplantation will receive treatment (AAT at 120mg/kg intravenously, based on Day -1 admission weight and rounded to the nearest 20mg) at the following time points:

• Day -1 prior to transplant

• Day 3 post-transplant

• Day 7 post-transplant

• Day 14 post-transplant Recipient management including the transplant procedure, postoperative care, immunosuppression and other medications, and post-transplant monitoring will follow standard of care protocols.

SCOPE & DURATION:

Recruitment will take place at the Clinical Islet Transplant Program at the University of Alberta Hospital, Edmonton, Alberta. Participants (N=12) will be adult patients, assessed and deemed appropriate to activate on the waiting list for islet transplantation. Anticipated duration of enrollment is 12 months, with follow-up at 90 days and 12 months.

In this pilot study control data will be obtained from a Standard of Care control cohort as comparison.

We will also obtain 2 year and 3 year long-term follow-up data from standard of care testing. This long-term follow up will review data collected within 3 years post-transplant and will include the following: patient and graft survival data, biochemical data from routine blood work, routine and for cause imaging, metabolic testing, initiation of interventions to treat complications, and reporting of any adverse or serious adverse events.

STUDY FOLLOWUP:

As follow-up, this study will use a number of blood tests and parameters used by the clinical program. We will obtain the following information regarding participant outcomes from routine blood testing, metabolic testing, and clinic visits:

• Complete blood count (CBC)-differential to monitor white and red blood cells

• Liver function tests

• Kidney function tests

• Blood sugar tests, including the Hemoglobin A1c (HbA1c) which estimates average blood sugars over 3 months.

• C-peptide testing, a chemical produced only be healthy, working islets.

These clinics will occur weekly x 4weeks, then at 1 month, 3 months, 6, months and 12 months. Participants will then have annual clinic visits, all as standard of care. Clinic visits include vital signs, physician assessment, review of recorded blood glucose records, and determination of patient requiring insulin or becoming insulin independent by a set of criteria based on the above blood sugar testing and glucose records. ;

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

• NCT number: NCT02520076
• Study type: Interventional
• Source: University of Alberta
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2015
• Completion date: September 30, 2019