Efficacy and Safety of Liraglutide in Subjects With Type 1 Diabetes Undergoing Islet Cell Transplantation

Study Overview
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Brief Summary
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This trial is conducted in Europe and North America. The aim of this trial is to investigate if liraglutide treatment can increase the proportion of insulin-independent subjects one year after islet cell transplantation who required only one (single-donor) islet cell transplant.

Official Title
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A 52 Week Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multi-Center, Multinational Trial In Islet Cell Transplant Subjects With Type 1 Diabetes Mellitus To Determine If The Early Use Of Liraglutide As An Adjunct To Standard Care Increases The Proportion Of Subjects Achieving Insulin Independence After First Transplantation

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes mellitus for at least 5 years Candidate for islet cell transplantation based upon local accepted practice and guidelines Reduced awareness of hypoglycaemia Exclusion Criteria: Treatment with any anti-diabetic medication other than insulin including insulin pump within 4 weeks of trial start Any previous organ transplantation A history of acute idiopathic or chronic pancreatitis Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br> | Drug: liraglutide<br>* Dose escalation of liraglutide up to 1.2 to 1.8 mg before islet cell transplant until the planned number of transplanted subjects is complete or subject is transplanted. After islet cell transplant, subjects continue to receive the reached liraglutide dose for 52 weeks. Injected subcutaneously(under the skin) once daily.<br>Drug: placebo<br>* Dose escalation escalation of liraglutide up to 1.2 to 1.8 mg before islet cell transplant until the planned number of transplanted subjects is complete or subject is transplanted. After islet cell transplant, subjects continue to receive the reached liraglutide placebo dose for 52 weeks. Injected subcutaneously (under the skin) once daily.<br>|
| Placebo Comparator: Liraglutide placebo<br> | Drug: placebo<br>* Dose escalation escalation of liraglutide up to 1.2 to 1.8 mg before islet cell transplant until the planned number of transplanted subjects is complete or subject is transplanted. After islet cell transplant, subjects continue to receive the reached liraglutide placebo dose for 52 weeks. Injected subcutaneously (under the skin) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant | Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant. | At week 52 after initial transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Hypoglycaemic Episodes | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and until the last day on randomised treatment. Confirmed hypoglycaemic episodes were categorised either as minor (PG<3.1 mmol/L [56 mg/dL]) or severe (subject unable to treat himself/herself). | During week 0 to week 52 | 
| Proportion of Subjects With HbA1c Below Or Equal to 6.5% At Week 52 That Are Free From Severe Hypoglycaemic Events | Proportion of subjects with HbA1c below or equal to 6.5% at week 52 that were free from severe hypoglycaemic events | From week 0 to week 52 after initial transplantation | 
| Proportion of Insulin-Independent Subjects | Proportion of insulin-independent subjects among all randomised subjects who had one or more transplantations after randomisation | At 52 weeks after initial transplantation | 
| Change in Islet Cell Yield During Culture | Change in islet cell yield from pre-culture to post-culture | From 0 hours pre-culture to 24 hours to 72 hours | 
| Glucose Level Variability And Hypoglycaemia Duration Derived From The Continuous Glucose Monitoring System (CGMS) | Change from baseline in glucose level variability and hypoglycaemia at baseline, weekly during liraglutide dose escalation, at 12 weeks pre-transplant, at 24 weeks post-transplant, 52 weeks post-transplant and 56 weeks (4 weeks after withdrawal of liraglutide or liraglutide placebo) | At 12 weeks pre-transplant, at 24 weeks post-transplant, 52 weeks post-transplant and 56 weeks (4 weeks after withdrawal of liraglutide or liraglutide placebo) |