Pancreatic Islet Transplantation in the Anterior Chamber of the Human Eye - a Pilot Study

Study Overview
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Brief Summary
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The overall objective is to establish that transplantation of allogeneic pancreatic islet cells into the anterior chamber of a severely visual impaired diabetic human eye is safe and does not cause ophthalmic or systemic complications. Furthermore, the change in insulin production, glucose control and hypoglycaemia awareness will be assessed.

Detailed Description
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Investigators intend to transplant 4 Type 1 Diabetes mellitus patients with compromised vision in one or both eyes due to diabetic or other complications, and who have already received kidney transplantation (i.e., already on immunosuppression). Transplantation of allogeneic pancreatic human islets will be performed into the anterior chamber of a single eye with compromised vision. Since the recipients are already immunosuppressed due to maintenance therapy for the kidney graft, investigators will only use non-steroidal anti-inflammatory drug (NSAID). Only in case of uncontrolled reaction, steroid should be used under guidance of the ophthalmologists. Investigators will neither inject local immunosuppressive drugs nor change ongoing immunosuppressive medication in the pilot study. The overall objective is to establish that transplantation of allogeneic pancreatic islet cells into the anterior chamber of a severely visual impaired diabetic human eye is safe and does not cause ophthalmic or systemic complications. Furthermore, the change in insulin production, glucose control and hypoglycaemia awareness will be assessed. In this pilot study investigators aim to gain experience in the technique, to obtain preliminary data on the amount of insulin that can be expected per transplanted islet equivalent (IEQ) and observe possible local reactions. These data will help to design a future larger study in patients without visual impairment.

Official Title
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Pancreatic Islet Transplantation in the Anterior Chamber of the Human Eye - a Pilot Study

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Procedure: Pancreatic islet transplantation in the anterior chamber


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 Diabetes (American Diabetes Association criteria) Kidney transplant recipient with ongoing immunosuppression At least one eye with extensive loss of vision from hand motion to no light perception due to damage of retina or optic nerve Age ≥ 18 years Normal cornea with good visualization of the anterior segment Patient not eligible or with no wish for standard pancreatic islet into the hepatic portal system or pancreas transplantation Exclusion Criteria: Uncontrolled diabetic retinopathy Signs of current infection Poor visualization of the anterior chamber

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pancreatic islet transplantation<br>Pancreatic islet transplantation in the anterior chamber of the human eye | Procedure: Pancreatic islet transplantation in the anterior chamber<br>* Transplantation of allogeneic pancreatic islet cells into the anterior chamber of a severely visual impaired diabetic human eye<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of ophthalmic complications | safety | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin production | Change in insulin production as derived from change in C-peptide, insulin, pro-insulin and glucose levels during the mixed meal tolerance test (MMTT) at Day 90 compared to baseline | 90 days | 
| Change in insulin requirements | Change in insulin requirements: 3-day average daily insulin dose at baseline compared to Day 90 (Day 87 through Day 89) | 90 days | 
| Change in HbA1c | Change in HbA1c levels from baseline (Day 0 pre-transplant) at Day 90 | 90 days | 
| Change in fasting glucose | Change in fasting glucose from baseline (Day 0 pre-transplant) at Day 90 | 90 days | 
| Change in total number of hypoglycemic events | Change in total number of hypoglycemic events 3-day average at baseline compared to Day 90 (Day 87 through Day 89) as assessed by continuous glucose monitoring (CGMS) | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic islet transplantation