11C-5-HTP PET in Clinical Islet Transplantation

Study Overview
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Brief Summary
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In people with type I diabetes, the insulin producing cells in the pancreas have been destroyed. Presently one can only evaluate the function of the graft through laboratory tests, blood sugars and the insulin requirements. The mass of the insulin producing cells and their location are not known. The possibility to study the mass of insulin producing cells is of importance when developing new treatment regimes, in order to evaluate their efficacy on this parameter. The researchers in this study are aiming to develop methods to measure the mass of insulin producing cells. A method (positron emission tomography, PET) previously used for the diagnosis of tumors of insulin producing cells may also be used to measure the amount of insulin producing cells in patients with type I diabetes. They plan to evaluate participants with type 1 diabetes that have undergone islet transplantation, to evaluate if PET can be used to measure the beta cell mass after islet transplantation.

Official Title
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Evaluation of the Use of 11C-5-HTP PET to Calculate βCell Mass in Clinical Islet Transplantation (DAIT CIT-09)

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Procedure: Positron-Emission Tomography
* Biological: 11C-5-HTP
* Procedure: Magnetic Resonance Imaging
* Procedure: Mixed-Meal Tolerance Test (MMTT)
* Procedure: Continuous Glucose Monitoring System® (CGMS)
* Procedure: Glomerular Filtration Rate Testing
* Procedure: Blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to be considered eligible for participation in the study: Subjects who are able to provide written informed consent and comply with the procedures of the study protocol. Patient that has received an islet transplant in or outside the CIT01 trial (post primary endpoint). Exclusion Criteria: Subjects who meet any of these criteria are not eligible for participation in the study: For female subjects: Positive serum pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures at the time of PET scan +/- 2 weeks. Known history of severe co-existing cardiac disease, characterized by any one of the following conditions: Recent myocardial infarction (within past 6 months). Evidence of ischemia on functional cardiac exam within the last year. Left ventricular ejection fraction <30%. Persistent elevation of liver function tests at the time of study entry. Persistent Aspartate Aminotransferase (serum glutamic-oxaloacetic transaminase), Alanine Aminotransferase (serum glutamate pyruvate transaminase), Alkaline phosphatase or total bilirubin, with values >1.5 times normal upper limits will exclude a patient. Treatment with any anti-diabetic medication, other than insulin, within 4 weeks of enrollment. Use of any investigational agents within 4 weeks of enrollment. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Positron-Emission Tomography|Dynamic scanning is performed for 60 minutes. Image acquisition is performed in 3D and reconstructed using an iterative OSEM VUEPOINT algorithm|
|Biological: 11C-5-HTP|150-400 MBq [11C]5-HTP (approximately 2-5 MBq/kg) is administered manually as an intravenous bolus in a intravenous catheter in the arm prior to PET imaging.|
|Procedure: Magnetic Resonance Imaging|Analysis will focus on adipose tissue distribution and composition in the liver.|
|Procedure: Mixed-Meal Tolerance Test (MMTT)|nan|
|Procedure: Continuous Glucose Monitoring System® (CGMS)|CGMS involves the subcutaneous (SC) placement of a glucose sensor connected by tubing to a pager-sized monitoring device that stores glucose data. Subjects will have the sensor placed in the clinic and wear it continuously for 72 - 84 hours (Gold) or 72-144 hours (iPro2).|
|Procedure: Glomerular Filtration Rate Testing|nan|
|Procedure: Blood draw|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The relationship between β cell mass calculated from the 11C-5-HTP PET scans and the MMTT C-peptide at 90 minutes | Regression methods will be used to describe the association between the beta cell mass and 90 minute c-peptide. | 8 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The relationship between βcell mass calculated from the 11C-5-HTP PET and the β-score computed at the time of the PET scan | Regression methods will also be used to develop models to describe the relationship between the number of islets infused and the islet mass measured by PET. | 8 month | 
| The relationship between βcell mass calculated from the 11C-5-HTP PET and CPGCR computed at the time of the PET scan |  | 8 month | 
| The relationship between βcell mass calculated from the 11C-5-HTP PET and number of islets transplanted (Total IEQ) |  | 8 month | 
| The distribution of islets in the liver | Descriptive measures and scatterplots will be used to visualize the distribution of beta cells in selected regions of the liver. | 8 month | 
| The distribution of fat accumulation in the liver |  | 8 month | 
| The relationship between distribution patterns in the liver and MMTT C-peptide at 90 minutes computed at the time of the PET scan |  | 8 month | 
| The relationship with PET and peak C-peptide |  | 8 month | 
| The relationship with PET and C-peptide AUC |  | 8 month | 
| The distribution of islets in the liver related to distribution of fat accumulation in the liver as measured by MRI | Descriptive measures and scatterplots will be used to visualize the association between beta cells and fat deposits in the liver. | 8 month | 
| The incidence and severity of adverse events related to the PET investigation including allergic reactions |  | 8 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Islet Transplantation, Positron Emission Tomography (PET) Computed Tomography (CT) imaging