Clinical trial NCT04949867: Dual-Hormone Closed-Loop Glucose Control in Adolescents With Type 1 Diabetes
Official title: Dual-Hormone Closed-Loop Glucose Control in Adolescents With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Technical University of Denmark
name: Herlev Hospital
First posted: 2021-07-02
Enrollment: 11
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A randomized, single-blinded, cross-over study of glycemic control during dual-hormone therapy compared with single-hormone therapy in adolescents with type 1 diabetes.
Primary purpose: TREATMENT

Brief summary: Objective:

To assess the efficacy and safety of an insulin-glucagon dual-hormone (DH) closed-loop system compared with an insulin-only single-hormone (SH) closed-loop system in adolescent with type 1 diabetes.

Methods:

In a 26-h, randomized, crossover, inpatient study, 20 children and adolescents with type 1 diabetes used two modes of the DiaCon Artificial Pancreas system: DH and SH closed-loop control. During each study period, participants will have one overnight stay, received three meals and performed exercise for 45 min (bicycle with estimated 50% V02max).

Endpoint:

The primary endpoint is sensor-derived percentage of time in hypoglycemia (\<3.9 mmol/L).

Detailed description: Upon arrival at the research facility at Steno Diabetes Center Copenhagen, the participant's own pump and CGM are disconnected, and the two study pumps are attached. For dual-hormone control, the study pumps will be filled with FiAsp® and GlucaGen®. For single-hormone control, the study pumps have been filled with FiAsp® and isotonic saline.

In addition, participants are provided with a blinded wearable activity and sleep monitoring device (ActiGraph GT9X Link, Pensacola, FL) for activity level estimation and sleep assessment during study participation. The Actigraph is connected to a Bluetooth® Polar heart rate monitors during the exercise session.

Female participants deliver a urine sample for pregnancy testing. A sampling cannula is placed in an antecubital vein. The CGM will be calibrated with fingerpick glucose meter (Contour next®, Ascensia Diabetes Care) before initiating the closed-loop control. Even though it is not needed to calibrate the sensor, the accuracy of the sensor is better after one calibration.

At day 1 17:00 the study is initiated, and the closed-loop system takes over glucose control. Except from the control approach (single- vs. dual-hormone), the study days are identical. During the study visit, participants can move around freely, but they can only perform actual exercise during the stationary bike exercise session at day 2 16:30. At nighttime, the participants are encouraged to be in bed and, if possible, sleep.

At predefined timepoints, the investigators measure blood pressure and pulse, and the investigators ask the participants to rate their nausea level on a visual analog scale (VAS) from 1 to 100 to assess possible side effects of glucagon (vomiting rates as 100). In addition, the investigators ask them to self-rate blood glucose levels before bedtime (23:00), upon wake-up (07:00-08:00), before each meal, before exercise, and every 10 minutes during exercise.

Single-hormone and dual-hormone closed-loop control study sessions end 26 hours after study start. The study pumps and the CGMs are disconnected and the participants reconnect their own pumps and CGMs.

The two study sessions are separated by at least 36 hours.

Eligibility criteria: Inclusion Criteria:

* Age = 13-17 years
* T1D duration ≥ 2 years
* Insulin pump therapy ≥ 1 year
* Using CGM or isCGM (Flash Libre)
* HbA1c ≤ 9.0% (75 mmol/mol)
* Using carbohydrate counting

Exclusion Criteria:

* Allergy to glucagon or lactose
* Allergy to faster insulin aspart (FiAsp)
* Pheochromocytoma
* Self-reported lack of hypoglycemia symptoms when blood glucose is \< 3.0 mmol/l
* Inability to follow study procedures, e.g. exercise, sleeping, blood sampling, and meal intake
* Pregnancy, nursing, plan to become pregnant or sexually active and not using adequate contraceptive methods (intrauterine device, contraceptive pill, patch or injection)
* Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during or within 30 days prior to study participation
* Other concomitant medical or psychological condition that according to the investigator's assessment makes the participant unsuitable for study participation

Primary outcomes:
measure: Percentage of time with glucose values < 3.9 mmol/l as measured by the continuous glucose monitor
timeFrame: 26 hours during closed-loop control
Secondary outcomes:
measure: Number of carbohydrate interventions to treat hypoglycemia
timeFrame: 26 hours during closed-loop control
measure: Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by continuous glucose monitor and plasma glucose
timeFrame: 26 hours during closed-loop control
measure: Percentage of time with glucose values < 3.9 mmol/l as measured by plasma glucose
timeFrame: 26 hours during closed-loop control
measure: Percentage of time with glucose values in the range > 13.9 mmol/l measured by continuous glucose monitor and plasma glucose
timeFrame: 26 hours during closed-loop control
measure: Percentage of time with glucose values < 3.0 mmol/l as measured by continuous glucose monitor and plasma glucose
timeFrame: 26 hours during closed-loop control
measure: Mean blood glucose value measured by continuous glucose monitor and plasma glucose
timeFrame: 26 hours during closed-loop control
measure: Number of hypoglycemic episodes < 3.9 mmol/l on continuous glucose monitor and plasma glucose
timeFrame: 26 hours during closed-loop control
measure: Continuous glucose monitored glycemic variability measured as SD
timeFrame: 26 hours during closed-loop control
measure: Continuous glucose monitored glycemic variability measured as CV
timeFrame: 26 hours during closed-loop control
measure: Composite outcome: Percentage of participants achieving (1) time in range (3.9-10) > 70 %, (2) time in alert hypoglycemia (<3.9 mmol/l) < 4 %, and (3) time in clinical hypoglycemia (<3.0 mmol) < 1% as measured by CGM and YSI
timeFrame: 26 hours during closed-loop control
measure: Total insulin dose
timeFrame: 26 hours during closed-loop control
measure: Total glucagon dose
timeFrame: 26 hours during closed-loop control
measure: Number of manual insulin boluses
timeFrame: 26 hours during closed-loop control
measure: Number of adverse events - Nausea
timeFrame: 26 hours during closed-loop control
measure: Number of adverse events - Headache
timeFrame: 26 hours during closed-loop control
measure: Number of adverse events - Palpitation
timeFrame: 26 hours during closed-loop control
measure: Number of vomits
timeFrame: 26 hours during closed-loop control
measure: Difference between actual and participant-estimated carbohydrate content in meals
timeFrame: 26 hours of closed-loop glucose control
measure: Mean Borg scale
timeFrame: During 45 minutes exercise
measure: Physical activity intensity measured by ActiGraph GT9X Link
timeFrame: 26 hours
measure: Sleep efficiency measured by ActiGraph GT9X Link
timeFrame: 26 hours
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Herlev
country: Denmark
facility: Herlev Hospital
Study officials:
References: