Type 1 Diabetes MellitusPhase 1NCT00453817
Islet of Langerhans Graft Monitoring by Magnetic Resonance Imaging
A Phase 1 study testing ferucarbotran (iron-based MRI contrast agent), Islet transplantation and Magnetic resonance imaging in people with Type 1 Diabetes Mellitus, run by University Hospital, Geneva at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- ferucarbotran (iron-based MRI contrast agent), Islet transplantation and Magnetic resonance imaging
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jun 2005to Jun 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients on the waiting list for an islet of Langerhans transplantation procedure
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Geneva University Hospitals Department of Surgery
Geneva, 1211
About this study
Official title: 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.
Read the 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.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- ferucarbotran (iron-based MRI contrast agent), Islet transplantation, Magnetic resonance imaging
- Keywords
- islet transplantation, imaging, graft monitoring, magnetic resonance imaging
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ferucarbotran (iron-based MRI contrast agent)Drug
islets will be incubated with ferucarbotran prior to transplantation, for imaging after transplantation
Islet transplantationProcedure or surgery
intraportal percutaneous islet transplantation
Magnetic resonance imagingProcedure or surgery
Magnetic resonance imaging of the liver before and after islet transplantation (6 days, 6 weeks, 6 months, 1 year)
| Study group | Role | What they receive |
|---|---|---|
| Study subjects | Experimental | One-arm observational study Receives: Drug: ferucarbotran (iron-based MRI contrast agent); Procedure: Islet transplantation; Procedure: Magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Semi-quantitative assessment of intrahepatic MRI signal on T2*-weighted sequences, at 6 days, 6 weeks, 6 months and 1 year after transplantation
Measured: 2005-2009
Secondary outcomes (1)
Islet graft function assessed by exogenous insulin requirements, HbA1c, mean amplitude of glucose excursions (MAGE) and fasting C-peptide.
Measured: 2005-2009
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2007 (estimated)
- Study startJun 2005
- Primary completionJun 2010
- Study completionJun 2010
Why it stopped: Feasibility issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thierry Berney, University Hospital, Geneva
- Investigators
- Thierry Berney, MD, MSc, Principal investigator, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00453817
- Sponsor's protocol ID
- 04-019
- Status last verified
- Dec 2014
- First submitted
- 4 Oct 2006
- Last updated
- 2 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Suivi Par résonance magnétique après Transplantation d'îlots de Langerhans
- ClinicalTrials.gov ID
- NCT00453817
- Acronym / sponsor ID
- 04-019
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- islet transplantation, imaging, graft monitoring, magnetic resonance imaging
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Feasibility issues
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Study start
- Jun 2005
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 29 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study subjects | Experimental | Drug: ferucarbotran (iron-based MRI contrast agent), Procedure: Islet transplantation, Procedure: Magnetic resonance imagingOne-arm observational study |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients on the waiting list for an islet of Langerhans transplantation procedure
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ferucarbotran (iron-based MRI contrast agent)islets will be incubated with ferucarbotran prior to transplantation, for imaging after transplantation | Drug | Study subjects |
| Islet transplantationintraportal percutaneous islet transplantation | Procedure or surgery | Study subjects |
| Magnetic resonance imagingMagnetic resonance imaging of the liver before and after islet transplantation (6 days, 6 weeks, 6 months, 1 year) | Procedure or surgery | Study subjects |
Primary outcome
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
1 secondary outcome
Islet graft function assessed by exogenous insulin requirements, HbA1c, mean amplitude of glucose excursions (MAGE) and fasting C-peptide.
Time frame: 2005-2009
Results and safety
The study was stopped early (reason given: Feasibility issues). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2014.
Related trials for Type 1 Diabetes Mellitus
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thierry Berney, MD, MSc principal investigator
University Hospital, Geneva
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ferucarbotran (iron-based MRI contrast agent), Islet transplantation and Magnetic resonance imaging in people with Type 1 Diabetes Mellitus, run by University Hospital, Geneva at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Feasibility issues). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2014.