Islet of Langerhans Graft Monitoring by Magnetic Resonance Imaging
Primary Purpose
Type 1 Diabetes Mellitus
Status
Terminated
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
ferucarbotran (iron-based MRI contrast agent)
Islet transplantation
Magnetic resonance imaging
Sponsored by
About this trial
This is an interventional diagnostic trial for Type 1 Diabetes Mellitus focused on measuring islet transplantation, imaging, graft monitoring, magnetic resonance imaging
Eligibility Criteria
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)
Sites / Locations
- Geneva University Hospitals Department of Surgery
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study subjects
Arm Description
One-arm observational study
Outcomes
Primary Outcome Measures
Semi-quantitative assessment of intrahepatic MRI signal on T2*-weighted sequences, at 6 days, 6 weeks, 6 months and 1 year after transplantation
Secondary Outcome Measures
Islet graft function assessed by exogenous insulin requirements, HbA1c, mean amplitude of glucose excursions (MAGE) and fasting C-peptide.
Full Information
NCT ID
NCT00453817
First Posted
October 4, 2006
Last Updated
December 1, 2014
Sponsor
University Hospital, Geneva
1. Study Identification
Unique Protocol Identification Number
NCT00453817
Brief Title
Islet of Langerhans Graft Monitoring by Magnetic Resonance Imaging
Official Title
Suivi Par résonance magnétique après Transplantation d'îlots de Langerhans
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Terminated
Why Stopped
Feasibility issues
Study Start Date
June 2005 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Geneva
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
Keywords
islet transplantation, imaging, graft monitoring, magnetic resonance imaging
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study subjects
Arm Type
Experimental
Arm Description
One-arm observational study
Intervention Type
Drug
Intervention Name(s)
ferucarbotran (iron-based MRI contrast agent)
Intervention Description
islets will be incubated with ferucarbotran prior to transplantation, for imaging after transplantation
Intervention Type
Procedure
Intervention Name(s)
Islet transplantation
Intervention Description
intraportal percutaneous islet transplantation
Intervention Type
Procedure
Intervention Name(s)
Magnetic resonance imaging
Intervention Description
Magnetic resonance imaging of the liver before and after islet transplantation (6 days, 6 weeks, 6 months, 1 year)
Primary Outcome Measure Information:
Title
Semi-quantitative assessment of intrahepatic MRI signal on T2*-weighted sequences, at 6 days, 6 weeks, 6 months and 1 year after transplantation
Time Frame
2005-2009
Secondary Outcome Measure Information:
Title
Islet graft function assessed by exogenous insulin requirements, HbA1c, mean amplitude of glucose excursions (MAGE) and fasting C-peptide.
Time Frame
2005-2009
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry Berney, MD, MSc
Organizational Affiliation
University Hospital, Geneva
Official's Role
Principal Investigator
Facility Information:
Facility Name
Geneva University Hospitals Department of Surgery
City
Geneva
ZIP/Postal Code
1211
Country
Switzerland
12. IPD Sharing Statement
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Islet of Langerhans Graft Monitoring by Magnetic Resonance Imaging
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