Islet of Langerhans Graft Monitoring by Magnetic Resonance Imaging

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by University Hospital, Geneva.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT00453817
First received: October 4, 2006
Last updated: June 25, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: ferucarbotran (iron-based MRI contrast agent)
Procedure: Islet transplantation
Procedure: Magnetic resonance imaging
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Suivi Par résonance magnétique après Transplantation d'îlots de Langerhans

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

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 [ Time Frame: 2005-2009 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Islet graft function assessed by exogenous insulin requirements, HbA1c, mean amplitude of glucose excursions (MAGE) and fasting C-peptide. [ Time Frame: 2005-2009 ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: June 2005
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    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)
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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00453817

Contacts
Contact: Thierry Berney, MD, MSc +41 22 37 23 404 thierry.berney@hcuge.ch
Contact: Sandrine Demuylder-Mischler, RN +41 22 37 27 759 sandrine.demuylder-mischler@hcuge.ch

Locations
Switzerland
Geneva University Hospitals Department of Surgery Recruiting
Geneva, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Thierry Berney, MD, MSc University Hospital, Geneva
  More Information

No publications provided

Responsible Party: Thierry Berney, MD, University of Geneva School of Medicine
ClinicalTrials.gov Identifier: NCT00453817     History of Changes
Other Study ID Numbers: 04-019
Study First Received: October 4, 2006
Last Updated: June 25, 2010
Health Authority: Switzerland: Swissmedic
Switzerland: Federal Office of Public Health

Keywords provided by University Hospital, Geneva:
islet transplantation
imaging
graft monitoring
magnetic resonance imaging

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Contrast Media
Ferumoxides
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014