Islet of Langerhans Graft Monitoring by Magnetic Resonance Imaging

Suivi Par résonance magnétique après Transplantation d'îlots de Langerhans

The primary objective of this pilot study is to assess the feasibility and safety of ex vivo islet labelling prior to intraportal transplantation in patients with type 1 diabetes with the purpose of islet graft imaging. The secondary objective is to determine the usefulness of this method for long-term islet graft monitoring.

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: ferucarbotran (iron-based MRI contrast agent); Procedure: Islet transplantation; Procedure: Magnetic resonance imaging

Detailed Description

The objectives will be addressed in a pilot study. We plan to enroll 15 patients over 3 years in islet transplantation alone (ITA), islet-after-kidney transplantation (IAK) or simultaneous islet-kidney transplantation (SIK) procedures. Patients will be followed-up for 1 year after transplantation.

Islet isolation and transplantation Islets will be isolated and purified from pancreata harvested from multiorgan donors, according to the automated method described by Ricordi, with local modifications. After isolation, islets will be cultured overnight at 37°C in CMRL medium. After overnight culture, islets will be changed to fresh medium containing carbodextran-coated iron oxide nanoparticles (Resovist; Schering, Baar, Switzerland), at a target concentration of 5ul/ml, with a total dose not exceeding 0.08 ml/kg body weight, and further cultured for a total of 48-72 hours at 25°C until transplantation. Islet transplantation will be performed by intraportal infusion of the islet preparation, using a transhepatic percutaneous approach. Patients will receive infusions of at least 5,000 IEQ/kg. A second islet infusion will be administered to patients who have not reached insulin independence after the first transplant.

Graft monitoring and follow-up Patients will be followed for 1 year after last islet infusion. MRI will be performed prior to, 6 days, 6 weeks, 6 months and 1 year after islet infusion. A standard MRI protocol will be adapted. Since transplanted islets are already iron-labeled, no injection of contrast media will be done during MRI examination, and MRI sequences will not be repeated. After a scout image, axial views of the liver will be acquired with a fast gradient echo T2* weighted sequence, a fast spin echo T2* weighted sequence, ultrashort echo time T2* weighted sequences, a spin echo T1 weighted sequence and in/out of phase fast gradient echo T1 weighted sequences. Iron-labeled islets will be visualized as a loss of signal on fast gradient echo T2* weighted sequence, and the islet mass will be assessed in a semi-quantitative fashion using a visual scale. Finally, ultrashort echo time sequences will be used to generate a T2 map. The amount of iron contained inside the transplanted islets will be quantified based on the T2 map and the correction for the distribution of the iron particles inside the liver.

Monitoring results will be compared to islet function assessed by routine tests: exogenous insulin requirement, C-peptide, HbA1c, fructosamine, arginine stimulation test. Results will be analyzed retrospectively for the first 2 years. According to results of the analysis, the investigators may decide to intervene proactively (i.e. administer antirejection therapy) in the last year of the study, whenever results suggestive of a dysfunction are observed.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1211
    • Geneva University Hospitals Department of Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients on the waiting list for an islet of Langerhans transplantation procedure

Exclusion Criteria:

• Allergy to ferucarbotran
• Inability to undergo MRI (patients carrying osteosynthesis material, pacemakers or other metallic devices)
• Claustrophobia (tolerance to MRI)
• Hemosiderosis/hemochromatosis (interference with MRI signal)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study subjects; One-arm observational study	Drug: ferucarbotran (iron-based MRI contrast agent); islets will be incubated with ferucarbotran prior to transplantation, for imaging after transplantation; Procedure: Islet transplantation; intraportal percutaneous islet transplantation; Procedure: Magnetic resonance imaging; Magnetic resonance imaging of the liver before and after islet transplantation (6 days, 6 weeks, 6 months, 1 year)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Semi-quantitative assessment of intrahepatic MRI signal on T2*-weighted sequences, at 6 days, 6 weeks, 6 months and 1 year after transplantation	2005-2009

Secondary Outcome Measures

Outcome Measure	Time Frame
Islet graft function assessed by exogenous insulin requirements, HbA1c, mean amplitude of glucose excursions (MAGE) and fasting C-peptide.	2005-2009

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Principal Investigator: Thierry Berney, MD, MSc, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: October 4, 2006
• First Submitted That Met QC Criteria: March 28, 2007
• First Posted (Estimate): March 29, 2007

Study Record Updates

• Last Update Posted (Estimate): December 2, 2014
• Last Update Submitted That Met QC Criteria: December 1, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; imaging; islet transplantation; graft monitoring
• 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: 04-019