Bone Marrow vs Liver as Site for Islet Transplantation

Study Overview
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Brief Summary
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The goal of this study is to evaluate safety and efficacy of bone marrow (BM) as site for pancreatic islet transplantationin humans. Our hypothesis is that BM represents a better site than liver (currently the location of choice for this procedure) thanks to its potential capacity to favor islet engraftment. To address our hypothesis we propose herein a randomized phase II trial to compare BM and liver as sites for islet transplantation in T1D patients.

Detailed Description
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The study is a phase II, single center, open label, pilot study. We will recruit 12 patients with T1D to be randomly (1:1) assigned to receive islet either into the liver through the portal venous circulation (standard procedure; arm A, n=6) or directly into the BM at the level of the iliac crest (arm B, n=6). Patients will be selected from those eligible for islet Tx based on local practice and guidelines.

Official Title
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Bone Marrow vs Liver as Site for Islet Transplantation in Patients With Type 1 Diabetes: Pilot Study to Evaluate Efficacy

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Biological: Human pancreatic islet transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diabetic patients eligible for pancreatic islet transplantation based on local accepted practice and guidelines. This includes at least: a)clinical history compatible with T1D with insulin-dependence for >5 years; b) undetectable stimulated (arginine or MMTT) C-peptide levels (<0.3 ng/mL) in the 12 months before transplant c)presence of severe hypoglycaemic events Exclusion Criteria: presence of hematologic disease

Ages Eligible for Study
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Minimum Age: 18 Years

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A: intraportal islet infusion<br>Patients will received islet into the liver through the portal venous circulation (standard procedure) | Biological: Human pancreatic islet transplantation<br> <br> |
| Experimental: B: intra BM islet infusion<br>Patients will received an intra BM islet infusion at the level of the iliac crest. The direct intra BM administration will be performed following the same procedures that our institution utilizes for administration of cord-blood cells in patients with acute leukemia (Lancet Oncol. 2008;9:831). The procedure is easy and reproducible: a standard needle for BM aspiration is inserted in the iliac crest and cells are gently infused. | Biological: Human pancreatic islet transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion under stimulation | basal and -10 to 120 min time course of glucose, C-pep levels and insulin derived from the mixed meal tolerance test | month 12 post-Tx | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of Adverse Events (AE) and Serious Adverse Events (SAE) |  | throughout the study up to 1 year after first transplant | 
| Insulin requirement | Change in average daily insulin requirements | month 1, 3, 6, 9, 12 post- transplant | 
| Islet function | change in HbA1c, Transplant Estimated Function (TEF) and fasting C-peptide levels | month 1, 3, 6, 9, 12 post-Tx | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes