Clinical trial NCT00453817: Islet of Langerhans Graft Monitoring by Magnetic Resonance Imaging
Official title: Suivi Par résonance magnétique après Transplantation d'îlots de Langerhans
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Keywords: islet transplantation
imaging
graft monitoring
magnetic resonance imaging
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2007-03-29
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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)

Primary outcomes:
measure: Semi-quantitative assessment of intrahepatic MRI signal on T2*-weighted sequences, at 6 days, 6 weeks, 6 months and 1 year after transplantation
timeFrame: 2005-2009
Secondary outcomes:
measure: Islet graft function assessed by exogenous insulin requirements, HbA1c, mean amplitude of glucose excursions (MAGE) and fasting C-peptide.
timeFrame: 2005-2009
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals Department of Surgery
Study officials:
affiliation: University Hospital, Geneva
name: Thierry Berney, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: