Type 1 Diabetes, Hypoglycemia
Conditions
Keywords
Type 1 Diabetes, Hypoglycemia, Exercise, Glucagon, Hybrid closed-loop system
Brief summary
The primary aim of the study is to evaluate the glucose response to low-dose glucagon (single 150 µg dose) administered immediately before aerobic exercise in individuals with AHCL-treated T1D.
Detailed description
The study consists of a screening visit (visit A) and two additional study visits (visit B and visit C) completed in a sequential order. During study visit B participants will receive s.c. administration of 150 ug glucagon prior to a 45-min moderate intensity continuous exercise session and subsequently continue into a 1-hour post-exercise observation period. During study visit C the exact same procedures will be followed with the omission of glucagon.
Interventions
DRUGGlucaGen
150 ug glucagon will be administered to the participants before exercise.
Sponsors
Steno Diabetes Center Copenhagen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Two-arm open-label intervention study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Type 1 diabetes ≥ 2 years * Use of AHCL system MiniMed 780G ≥ 4 weeks * Use of Novorapid for ≥ 1 week
Exclusion criteria
* Allergies to lactose or glucagon * Known or suspected allergies to glucagon or related products * History of hypersensitivity or allergic reaction to glucagon or lactose * Patients with diagnosed pheochromocytoma, insulinoma or gastroparesis * Concomitant medical or psychological conditions identified through review of medical history, physical examination and clinical laboratory analysis that, according to the investigator's assessment, makes the individual unsuitable for study participation * Lack of compliance with key study procedures at the discretion of the investigator * Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (methods are considered adequate for study enrolment for females: an intrauterine device, hormonal contraception (birth control pills, implant, patch, vaginal ring or injection), a single partner who is sterile or infertile, or sexual abstinence. Contraception is required throughout the study duration. Sterilized or postmenopausal women (\>12 months since last period) are not required to use contraception) * Inability to understand the individual information and to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Percentage of Time in Target Glucose Range (PG: 3.9 - 10.0 mmol/l) During and for 1-hour After Dynamic Physical Exercise Between Visit B and C | 0 min to +105 min | This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Time (Min) to Hypoglycaemia (PG<3.9 mmol/l) Between Visit B and C | 0 min to +105 min | This outcome measure evaluates the time (in minutes) taken to reach hypoglycemia during a specified monitoring period or following a specific intervention. |
| Difference in Percentage of Time Below Target Glucose Range (PG<3.9 mmol/l) Between Visit B and C | 0 min to +105 min | This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study. |
| Difference in Percentage of Time Above Target Glucose Range (PG>10.0 mmol/l) Between Visit B and C | 0 min to +105 min | This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study. |
| Difference in Incidence Rate of Hyperglycaemia (PG>10.0 mmol/l) Between Visit B and C | 0 min to +105 min | This outcome measure assesses the incidence rate of hyperglycemia during a specified monitoring period. |
| Difference in Nadir PG Concentration Between Visit B and C | 0 min to +105 min | This outcome measure assesses the difference in the lowest value of plasma glucose during a specified monitoring period. |
| Difference in Incidence Rate of Hypoglycaemic Events (PG<3.9 mmol/l) Between Visit B and C | 0 min to +105 min | This outcome measure assesses the frequency of hypoglycemic events experienced by participants over a specified monitoring period. |
| Difference in Incremental Peak PG Concentration Between Visit B and C | 0 min to +105 min | This outcome measure assesses the difference in incremental peak of plasma glucose during a specified monitoring period. |
| Difference in Mean PG Concentration Between Visit B and C | 0 min to +105 min | This outcome measure assesses the difference in mean plasma glucose during a specified monitoring period. |
| Difference in PG Area Under the Curve (AUC) Between Visit B and C | 0 min to +105 min | This outcome measure assesses the difference in plasma glucose AUC during a specified monitoring period. |
| Difference in Standard Deviation in PG Concentrations Between Visit B and C | 0 min to +105 min | This outcome measure assesses the difference in SD plasma glucose during a specified monitoring period. |
| Difference in Coefficient of Variation in PG Concentrations Between Visit B and C | 0 min to +105 min | This outcome measure assesses the difference in CV in plasma glucose during a specified monitoring period. |
| Difference in Peak PG Concentration Between Visit B and C | 0 min to +105 min | This outcome measure assesses the difference in peak plasma glucose during a specified monitoring period. |
Countries
Denmark
Participant flow
Pre-assignment details
This is a cross-over study. A total of 10 unique participants were enrolled and assigned to both arms sequentially. Therefore, the number of participants started in each arm is 10, but these represent the same individuals. We initially planned for 16 participants, but only 10 participants completed both visits.
Participants by arm
| Arm | Count |
|---|---|
| 150 µg Glucagon Before Exercise Then No Glucagon Administered Before Exercise All participants received 150 µg Glucagon before exercise during Visit B, followed by a control condition (no glucagon) during Visit C in a fixed sequence | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | 150 µg Glucagon Before Exercise Then No Glucagon Administered Before Exercise | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 1 Participants | — |
| Age, Categorical Between 18 and 65 years | 9 Participants | — |
| Age, Continuous | 50 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Denmark | 10 participants | — |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Difference in Percentage of Time in Target Glucose Range (PG: 3.9 - 10.0 mmol/l) During and for 1-hour After Dynamic Physical Exercise Between Visit B and C
This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Percentage of Time in Target Glucose Range (PG: 3.9 - 10.0 mmol/l) During and for 1-hour After Dynamic Physical Exercise Between Visit B and C | 100 Percentage of time in range |
| Control | Difference in Percentage of Time in Target Glucose Range (PG: 3.9 - 10.0 mmol/l) During and for 1-hour After Dynamic Physical Exercise Between Visit B and C | 100 Percentage of time in range |
Secondary
Difference in Coefficient of Variation in PG Concentrations Between Visit B and C
This outcome measure assesses the difference in CV in plasma glucose during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Coefficient of Variation in PG Concentrations Between Visit B and C | 12.3 Percentage of variation | Standard Deviation 4.3 |
| Control | Difference in Coefficient of Variation in PG Concentrations Between Visit B and C | 7.3 Percentage of variation | Standard Deviation 2.5 |
Secondary
Difference in Incidence Rate of Hyperglycaemia (PG>10.0 mmol/l) Between Visit B and C
This outcome measure assesses the incidence rate of hyperglycemia during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Incidence Rate of Hyperglycaemia (PG>10.0 mmol/l) Between Visit B and C | 0 participants |
| Control | Difference in Incidence Rate of Hyperglycaemia (PG>10.0 mmol/l) Between Visit B and C | 0 participants |
Secondary
Difference in Incidence Rate of Hypoglycaemic Events (PG<3.9 mmol/l) Between Visit B and C
This outcome measure assesses the frequency of hypoglycemic events experienced by participants over a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Incidence Rate of Hypoglycaemic Events (PG<3.9 mmol/l) Between Visit B and C | 0 Participants |
| Control | Difference in Incidence Rate of Hypoglycaemic Events (PG<3.9 mmol/l) Between Visit B and C | 0 Participants |
Secondary
Difference in Incremental Peak PG Concentration Between Visit B and C
This outcome measure assesses the difference in incremental peak of plasma glucose during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Incremental Peak PG Concentration Between Visit B and C | 1.8 mmol/l |
| Control | Difference in Incremental Peak PG Concentration Between Visit B and C | -0.6 mmol/l |
Secondary
Difference in Mean PG Concentration Between Visit B and C
This outcome measure assesses the difference in mean plasma glucose during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Mean PG Concentration Between Visit B and C | 8.3 mmol/l | Standard Error 1.8 |
| Control | Difference in Mean PG Concentration Between Visit B and C | 6.7 mmol/l | Standard Error 1.3 |
Secondary
Difference in Nadir PG Concentration Between Visit B and C
This outcome measure assesses the difference in the lowest value of plasma glucose during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Nadir PG Concentration Between Visit B and C | 5.8 mmol/l |
| Control | Difference in Nadir PG Concentration Between Visit B and C | 5.8 mmol/l |
Secondary
Difference in Peak PG Concentration Between Visit B and C
This outcome measure assesses the difference in peak plasma glucose during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Peak PG Concentration Between Visit B and C | 9.3 mmol/l | Standard Deviation 1.8 |
| Control | Difference in Peak PG Concentration Between Visit B and C | 7.5 mmol/l | Standard Deviation 1.4 |
Secondary
Difference in Percentage of Time Above Target Glucose Range (PG>10.0 mmol/l) Between Visit B and C
This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Percentage of Time Above Target Glucose Range (PG>10.0 mmol/l) Between Visit B and C | 0 percentage of time above range |
| Control | Difference in Percentage of Time Above Target Glucose Range (PG>10.0 mmol/l) Between Visit B and C | 0 percentage of time above range |
Secondary
Difference in Percentage of Time Below Target Glucose Range (PG<3.9 mmol/l) Between Visit B and C
This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Percentage of Time Below Target Glucose Range (PG<3.9 mmol/l) Between Visit B and C | 0 percentage of time below range |
| Control | Difference in Percentage of Time Below Target Glucose Range (PG<3.9 mmol/l) Between Visit B and C | 0 percentage of time below range |
Secondary
Difference in PG Area Under the Curve (AUC) Between Visit B and C
This outcome measure assesses the difference in plasma glucose AUC during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in PG Area Under the Curve (AUC) Between Visit B and C | 824.2 mmol/l*min |
| Control | Difference in PG Area Under the Curve (AUC) Between Visit B and C | 686.2 mmol/l*min |
Secondary
Difference in Standard Deviation in PG Concentrations Between Visit B and C
This outcome measure assesses the difference in SD plasma glucose during a specified monitoring period.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Standard Deviation in PG Concentrations Between Visit B and C | 1.0 mmol/l |
| Control | Difference in Standard Deviation in PG Concentrations Between Visit B and C | 0.5 mmol/l |
Secondary
Difference in Time (Min) to Hypoglycaemia (PG<3.9 mmol/l) Between Visit B and C
This outcome measure evaluates the time (in minutes) taken to reach hypoglycemia during a specified monitoring period or following a specific intervention.
Time frame: 0 min to +105 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 ug Glucagon Before Exercise | Difference in Time (Min) to Hypoglycaemia (PG<3.9 mmol/l) Between Visit B and C | NA minutes |
| Control | Difference in Time (Min) to Hypoglycaemia (PG<3.9 mmol/l) Between Visit B and C | NA minutes |