Health Economic Analysis of Islet Cell Transplantation for the Stabilization of the Severe Forms of Type 1 Diabetes

Study Overview
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Brief Summary
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The main goal is to perform a cost-utility analysis to compare islet cell transplantation versus best medical treatment (defined as Sensor augmented pump therapy) for patients with brittle type1 diabetes.

Detailed Description
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The main goal is to perform a cost-utility analysis to compare islet cell transplantation versus best medical treatment (defined as Sensor augmented insulin pump therapy) for patients with brittle type1 diabetes.

Official Title
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Health Economic Analysis of Islet Cell Transplantation for Patients With Severe Forms of Brittle Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Procedure: Islet graft
* Drug: best medical care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Suffering from diabetes since more than 5 years Patient with brittle type 1 diabetes despite an optimized insulin treatment and educational training will be included. A patient will be considered as experiencing a brittle type 1 diabetes if at least two criteria are present among: persistence of severe hypoglycemia, occurrence of ketoacidosis events without obvious etiology, diagnosis of unaware hypoglycemic episodes < 3 mmol/l based on CGM or self-monitoring blood glucose data, a mean blood glucose standard deviation>50%, MAGE index (Mean amplitude of glucose excursions)>60 mg/dl, LBGI index (low blood glucose index)>5, Clarke score≥4 or HYPOSCORE>800. Insulin needs < 0,85 U/kg/day HbA1c < 12% ; No residual insulin secretion (plasmatic basal and stimulated C-peptide < 0.3 ng/ml) Social Security membership or benefit from Social Security Patients who signed the consent form Exclusion Criteria : Exclusion criteria related to islet infusion: Hemostatic disorders, pre-existing liver disease (PAL, Gamma-GT, ASAT-ALAT >2N) or vesicular lithiasis. Exclusion criteria related to diabetic complications: Evolutive proliferative retinopathy, evolutive nephropathy (Glomerular filtration rate <30 ml/min/1.73m2 and/or proteinuria >0.5g/day), evolutive cardiopathy or obliterative arteriopathy with trophic cutaneous lesions. Exclusion criteria related to immunosuppressant use: Hemoglobin < 110mg/dL in women and < 120 mg/dL in men, leuconeutropenia, thrombopenia, systemic infection including chronic hepatitis B, C and VIH, neoplasia disease and hypertension>160/100 mmHg. Corticoid treatment (except for patient that benefited from a kidney graft with maintenance steroid therapy) Presence of anti-HLA antibody directed against the donor Positive B or T cells crossmatch

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: Islet graft<br>Patients who receive islet graft Intervention : Procedure/Surgery | Procedure: Islet graft<br>* Patients will be transplanted with pancreatic islet cells<br>* Other names: islet cell transplantation;|
| Active Comparator: Best medical care<br>Patients who continue their optimal medical treatment (insulin pump therapy coupled with real time continuous glucose monitoring) Intervention : insulin treatment | Drug: best medical care<br>* Patients will continue their insulin treatment<br>* Other names: insulin treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental cost- utility ratio at 1 year | The primary endpoint will be the incremental cost-effectiveness ratio at one year for islet transplantation versus Best Medical Treatment of brittle type 1 diabetes.The effectiveness will be expressed as quality adjusted life years (QALYs) in a cost-utility analysis. QALYs are a composite measure of outcomes where utilities for health states (on 0-1 scale, where 0 corresponds to death and 1 to full health) act as qualitative weights to combine quantity and quality of life. The number of QALYs in each group will be assessed with the EuroQol 5 Dimensions questionnaire (EQ5D). The EQ-5D measures health status in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost-effectiveness ratio at 1 year | Assessment of the cost-effectiveness ratio at 1 year between islet cell transplantation versus best medical treatment (SAP therapy) for patients with brittle type 1 diabetes without impairment of vital prognosis. Two criteria of effectiveness will be used : the life years gained and the number of hypoglycemia | 1 year | 
| Assessment of individual medical benefit of quality of life | Evaluate with DQOL questionnaire | 6 months and 1year | 
| Assessment of individual medical benefit in terms of metabolic efficacy | measured from the following criteria: severe hypoglycemia, HbA1c, stimulated C-peptide, fasting glucose, insulin dose or oral diabetes, glycemic variability | 6 months and 1 year | 
| Assessment and comparison of individual medical benefit in terms of complications of islet cell transplantation between the two groups | measured from in insulin independence, hospitalizations | 6 months and 1 year | 
| Assessment and comparison of clinical benefit for patients with brittle type 1 diabetes with impairment of vital prognosis before and after islet cell transplantation | measured from DQOL, insulin independence, complications of islet cell transplantation | 1 year | 
| Assessment and comparison of costs for patients with brittle type 1 diabetes with impairment of vital prognosis before and after islet cell transplantation | measured from hospitalizations | 1 year | 
| Assessment of total cost of islet cell transplantation | Assessment of total cost of islet cell transplantation for patients with type 1 diabetes without impairment of vital prognosis, from pre-transplant period until 1 year after the last injection. Two perspectives will be used: French health care system and hospital. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cost-utility analysis, Type 1 Diabetes, Islet cell Transplantation, cost-effectiveness analysis