Type 1 Diabetes
Conditions
Keywords
Ultra rapid-acting insulin, Lyumjev, Humalog®, Artificial pancreas (AP®), Bihormonal reactive closed loop system, Automated glucose regulation, Time above range
Brief 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 (%).
Interventions
DRUGInsulin Lispro Cartridge [Lyumjev]
Administration of Lyumjev in combination with the AP system
DRUGInsulin Lispro Cartridge
Administration of Humalog in combination with the AP system (standard therapy)
Sponsors
Inreda Diabetic B.V.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
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))
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with diabetes mellitus type 1; * Treated with the Inreda AP system for a minimum of 1 month; * Age between 18 and 75 years; * Willing and able to sign informed consent. Since subjects are treated with the Inreda AP, the following inclusion criteria will be met: * Treated with sensor augmented pump (SAP) or CSII for a minimum of 6 months; * HbA1c \< 97 mmol/mol; * BMI \< 35 kg/m\^2; * No use of acetaminophen, as this may influence the sensor glucose measurements.
Exclusion criteria
* Impaired awareness of hypoglycemia (score ≥ 4) according to Gold and/or Clarke questionnaire; * Pregnancy and/or breastfeeding; * Use of oral antidiabetic agents; * Insulinoma; * Hypersensitivity reactions to Lyumjev or any of the excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time the Glucose Level is Above 10 mmol/l | 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 | Time the glucose level is above range (\>10 mmol/l) expressed as a percentage (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Parameters: Mean Glucose Value | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Mean of the glucose values (parameter required to determine the coefficient of variation) |
| Side Effects of Insulin | 68 days (whole study period) | Side effects of insulin (each reported side effect of Humalog and Lyumjev) |
| Pharmacodynamic Parameters: Euglycemia | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Percentage of time the glucose level is between 3.9 and 10 mmol/l (%) |
| Pharmacodynamic Parameters: Standard Deviation of Glucose Value | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Standard deviation of the glucose values (parameter required to determine the coefficient of variation) |
| Pharmacodynamic Parameters: Glycemic Variability (CoV) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Glycemic variability expressed as the coefficient of variation (CoV): standard deviation divided by the mean of the glucose values (%) |
| Pharmacodynamic Parameters: Glycemic Variability (IQR) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Glycemic variability expressed as the interquartile range (IQR) (mmol/l) |
| AP-related Parameters: Daily Insulin Usage (Units) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Daily insulin usage (units) |
| AP-related Parameters: Glucagon Usage | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Daily usage of glucagon (mg) |
| Pharmacodynamic Parameters: Hypoglycemia | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Percentage of time the glucose level is below 3.9 mmol/l (%) |
| AP-related Parameters: Algorithm Activity | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) | Percentage of time the algorithm is active (%) |
Countries
Netherlands
Contacts
PRINCIPAL_INVESTIGATORA. van Bon, MD, PhD
Rijnstate Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| BMI N=12 | 26.0 kg/m^2 STANDARD_DEVIATION 4.2 |
| BMI N=7 (included in analysis) | 25.0 kg/m^2 STANDARD_DEVIATION 4.3 |
| Diabetes duration N=12 | 20.5 years |
| Diabetes duration N=7 (included in analysis) | 17.0 years |
| HbA1c N=12 | 50.5 mmol/mol |
| HbA1c N=7 (included in analysis) | 51.0 mmol/mol |
| Region of Enrollment Netherlands | 12 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
None listed