Ultrarapid Insulin Administered by a Bihormonal Closed Loop System in Patients With Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      The main objective is to determine the efficacy of Lyumjev (insulin) in a bi-hormonal
      reactive closed loop system for automated glucose regulation (artificial pancreas; AP®) in
      patients with diabetes mellitus type 1. In addition, safety parameters, pharmacodynamics and
      AP-related parameters will be acquired.

      This study is a multicenter, open-label, randomized, cross-over trial in 12 subjects. The
      subjects will be randomized to receive either Lyumjev or Humalog® for a 30-day study period
      and will then switch to the alternate insulin treatment after a wash-out period.
    

Detailed description: 
      Background of the study:

      Inreda Diabetic B.V. (Goor, The Netherlands) developed a bi-hormonal reactive closed loop
      system to automate glucose regulation (artificial pancreas; AP) in patients with diabetes
      mellitus type 1. In the current CE-marked AP, Humalog® (Eli Lilly) is used as rapid-acting
      insulin. Currently, the ultra rapid-acting insulin Lyumjev (Eli Lilly) is available but has
      not yet been tested in combination with the AP of Inreda. Both are insulin lispro, but
      additions to the insulin lispro allow the insulin to act faster with a shorter duration. The
      hypothesis is that the combination of Lyumjev and the reactive AP system can decrease the
      time that glucose values are above range which can have a positive effect on glucose
      regulation.

      Objectives of the study:

      The main objective is to determine the efficacy of Lyumjev in the Inreda AP system. Secondary
      objectives are to assess safety parameters, differences in pharmacodynamics and AP-related
      outcomes comparing Lyumjev to Humalog®.

      Study design:

      This study is a multicenter, open-label, randomized, cross-over trial which will be performed
      in a free-living environment.

      Study population:

      The study population will comprise 12 subjects with diabetes type 1 using the AP system.
      Inclusion criteria are subjects from 18 to 75 years and treated with the Inreda AP system for
      at least 1 month.

      Intervention:

      The intervention includes the administration of Lyumjev by the Inreda AP system. The subject
      will be randomized to receive either Lyumjev or Humalog® during the first 30 days. After a
      wash-out period of 8 days using the standard insulin Humalog®, the subject will switch to the
      alternate treatment, again for a 30-day period. During the study periods, subjects have to
      keep a Wi-Fi access point with them.

      Primary study parameters/outcome of the study:

      Main parameter to express efficacy is the time above range (>10.0 mmol/l), which will be
      compared between Lyumjev and Humalog®.

      Secondary study parameters/outcome of the study:

      Safety will be expressed as the side effects of Lyumjev. Pharmacodynamics will be expressed
      in proportions of time spent in eu-/hypo-/hyperglycemia (%), median glucose value (mmol/l)
      and glycemic variability (% and interquartile range). These parameters will all be compared
      between Lyumjev and reference Humalog®.

      AP-related outcomes will be expressed in daily administered dosage of insulin and glucagon
      (units), and the percentage of time that the closed loop algorithm is active (%).
    

Intervention name(s): Insulin Lispro Cartridge [Lyumjev]; Insulin Lispro Cartridge
Intervention type(s): Drug; Drug
Intervention description(s): Administration of Lyumjev in combination with the AP system; Administration of Humalog in combination with the AP system (standard therapy)
Other intervention name(s): Lyumjev; Humalog
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Lispro
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Allocation by randomization:
Study period 1 (Humalog or Lyumjev)
Wash-out period (Humalog: standard therapy)
Study period 2 (other type of insulin than in Study period 1 (Humalog or Lyumjev))
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ultra rapid-acting insulin; Lyumjev; Humalog®; Artificial pancreas (AP®); Bihormonal reactive closed loop system; Automated glucose regulation; Time above range