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.
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 (%).
Administration of Lyumjev in combination with the AP system
Administration of Humalog in combination with the AP system (standard therapy)
Rijnstate Hospital
Arnhem, Gelderland, Netherlands
Slingeland Hospital
Doetinchem, Gelderland, Netherlands
Hospital Gelderse Vallei
Ede, Gelderland, Netherlands
Percentage of Time the Glucose Level is Above 10 mmol/l
Time the glucose level is above range (\>10 mmol/l) expressed as a percentage (%)
Time frame: 25 days for each intervention period (50 days in total); 5-day training period and washout period were excluded from analysis; data were continuously acquired
Side Effects of Insulin
Side effects of insulin (each reported side effect of Humalog and Lyumjev)
Time frame: 68 days (whole study period)
Pharmacodynamic Parameters: Euglycemia
Percentage of time the glucose level is between 3.9 and 10 mmol/l (%)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
Pharmacodynamic Parameters: Hypoglycemia
Percentage of time the glucose level is below 3.9 mmol/l (%)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
Pharmacodynamic Parameters: Mean Glucose Value
Mean of the glucose values (parameter required to determine the coefficient of variation)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
Pharmacodynamic Parameters: Standard Deviation of Glucose Value
Standard deviation of the glucose values (parameter required to determine the coefficient of variation)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Pharmacodynamic Parameters: Glycemic Variability (CoV)
Glycemic variability expressed as the coefficient of variation (CoV): standard deviation divided by the mean of the glucose values (%)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
Pharmacodynamic Parameters: Glycemic Variability (IQR)
Glycemic variability expressed as the interquartile range (IQR) (mmol/l)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
AP-related Parameters: Daily Insulin Usage (Units)
Daily insulin usage (units)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
AP-related Parameters: Glucagon Usage
Daily usage of glucagon (mg)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)
AP-related Parameters: Algorithm Activity
Percentage of time the algorithm is active (%)
Time frame: 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired)