Objective
the STABILOOP study aims at analyzing if CL therapy may be a suitable therapeutic option for patients theoretically candidates for islet transplantation and allow patients to reach optimal glycemic control while avoiding risk of islet transplantation.
Primary objective of the study is to describe the proportion of patients in whom CL therapy has failed to rule out glycemic issues. Secondary objectives are to describe the durability of closed loop efficacy, to compare the quality of glycemic control and quality of life obtained after equipment by CL therapy in patients stabilized by CL therapy as compare to patients addressed to IT after failure of CL, to analyze security of CL therapy to identify predictive factors of success/failure of CL therapy, to conduct an exploratory medico-economic analysis of the strategies.
Background Rationale
Some patients living with type 1 diabetes, despite a well conducted optimal insulin treatment and education, describe major glycemic lability with frequent and unpredictable severe hypoglycemia (SH) leading to dramatic impairment of their quality of life, exposing patient to hypoglycemic coma and vital risk. For these patients, islet transplantation (IT) can be proposed. Islet transplantation is now reimbursed in France for patients living with type 1 diabetes and functional kidney graft if patients HbA1c >7% and/or if they are experiencing severe hypoglycemia (Islet after kidney candidate population). Islet transplantation is also reimburse in patients living with type 1 diabetes and experiencing extreme glycemic variability associated with unpredictable clinical and metabolic events impairing quality of life such as severe, disabling and frequent hypoglycemia (At least 2 severe hypolycemia in the last 12 months and at least 1 life-threatening severe in the last 12 months (coma or convulsions or trauma) or keto-acidosis. Islet transplantation has demonstrated benefits in terms of glycemic stabilization, prevention of severe hypoglycemia, improvement of quality of life but its morbidity is not null (risk of hemorrhagic complications, portal thrombosis and chronic immunosuppression). Closed-loop devices (CL) have emerged and demonstrated improved glycemic control in type 1 diabetic patients but the efficacy of these CL devices in patients living with a unstable type 1 diabetes, candidates for islet transplantation has been poorly evaluated. Only one study showed a benefit in terms of glycemic stabilization in these patients. Now that CL therapy is the new gold standard treatment of patients with type 1 diabetes, it is important to positionate CL in the care pathway of patient’s candidate for IT.
Description of Project
Some patients living with type 1 diabetes, despite a well conducted optimal insulin treatment and education, describe major glycemic variability with frequent and unpredictable severe hypoglycemia (SH) leading to dramatic impairment of their quality of life, exposing patient to hypoglycemic coma and vital risk. For these patients, islet transplantation (IT) can be proposed and is now reimbursed in France. Islet transplantation permit to stabilize glycemia, protect patients against occurence of severe hypoglycemia, improve quality of life and sometimes allow obtention of transient insulin independency. Nevertheless, islet transplantation exposed patients to risks (risk of hemorrhage, portal vein thrombosis , risk of infection and cancers due to chronic immunosuppressive therapy required for transplantation ). Closed-loop devices (CL) have emerged over the last year and improved glycemic control in type 1 diabetic patients but the efficacy of these CL devices in patients living with an unstable type 1 diabetes, candidates for islet transplantation has been poorly evaluated. Only one study showed a benefit in terms of glycemic stabilization in these patients. Now that CL therapy is the new gold standard treatment of patients with type 1 diabetes, it is important to positionate CL in the care pathway of patient’s candidate for IT. In this context, the STABILOOP study will analyze if CL therapy may be a suitable therapeutic option for patients theoretically candidates for islet transplantation and allow patients to reach optimal glycemic control while avoiding risk of islet transplantation. STABILOOP study will be a french prospective, multicentric, descriptive cohort involving clinical centers with an expertise both in islet transplantation and closed loop therapy (Grenoble, Lyon, Strasbourg, Montpellier, Paris, Toulouse). All patients addressed at centers for islet transplantation will be evaluated for IT, proposed to be a part of the present cohort and included in the cohort in absence of patient opposition. Patients will be proposed to be trained and equipped with closed loop therapy and to follow a specific structured educational program to address glycemic variability. After closed loop initiation and educational program, patients will be followed as standard care. Quality of glycemic control (each 3 months) and quality of life (each 6 months the first year and then yearly) will be evaluated. In case of persistence or recurrence of metabolic criteria requiring islet transplantation, patients will be registered for islet transplantation waiting list, transplanted and followed as standard care. In case of disappearance of metabolic criteria requiring islet transplantation after closed loop therapy initiation, patients will continue closed loop therapy and will be followed-up each 3 months. At any time during the follow-up, if a recurrence of metabolic criteria requiring islet transplantation is observed, patients will be registered for islet transplantation waiting list, transplanted and followed as standard care. Primary objective of the study is to describe the proportion of patients in whom CL therapy has failed to rule out glycemic issues. Secondary objectives are to describe the durability of closed loop efficacy, to compare the quality of glycemic control and quality of life obtained after equipment by CL therapy in patients stabilized by CL therapy as compare to patients addressed to IT after failure of CL, to analyze security of CL therapy to identify predictive factors of success/failure of CL therapy, to conduct an exploratory medico-economic analysis of the strategies.
Anticipated Outcome
Based on study results of closed loop therapy obtained in clinical trial L or real-life study in which nearly 2/3 of patients achieved recommended international goals for glycemic control, we assume a same proportion of achievement of optimal glycemic control in the population of patients with kidney graft allowing to avoid islet transplantation in ⅔ of this population. Based on the results of DBLHU study (a study that analyse the efficacy of the DBLHU closed loop therapy in patients with unstable type 1 diabetes) within only 1 patient among the 7 participants failed to be protected from severe hypoglycemia, we expected such results in the population of patients with severe glycemic variability and severe hypoglycemia. STABILOOP project will permit to precise the place of closed loop therapy in the pathway care of patients currently candidates for islet transplantation, to probably place closed loop therapy as the ultimate step before IT and restricted islet transplantation only to patients in whom closed therapy failed to achieve optimal glycemic control or prevented severe hypoglycemia. It will refine the benefit-risk ratio of close loop therapy and Islet transplantation in such a population.
Relevance to T1D
Diabetes with High glycemic variability, severe hypoglycemia and hypoglycemic coma if rare are a huge burden for patients living with type 1 diabetes. To identify the efficacy of closed loop therapy in patients living with this such sever form of diabetes is mandatory in order to propose or not closed loop therapy to these patients. If closed loop therapy is efficient to stabilize glycemic control and avoid severe hypoglycemia, our study will permit to avoid the risk of islet transplantation.