Dual-Hormone Closed-Loop Glucose Control in Adolescents With Type 1 Diabetes

Type 1 Diabetes Clinical Trial

— DHCL2021  

Official title:

Dual-Hormone Closed-Loop Glucose Control in Adolescents With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04949867
• Other study ID #: H-21000207
• Secondary ID: 2020-005836-3120
• Status: Completed
• Phase: Phase 4
• Start date: May 20, 2021
• Est. completion date: April 26, 2022

Study information

• Verified date: August 2022
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: April 26, 2022
• Est. primary completion date: April 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Glucagon
Glucagon is filled in the pump and given automatically in case of hypoglycemia or pending hypoglycemia.

Device:
• Closed-loop System
Closed-loop system comprise of two DANA RS (R) insulin pumps (FiAsp-GlucaGen vs FiAsp-saline), one DexCom G6 sensor, and a smartphone for the control algorithm.

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Copenhagen	Gentofte
Denmark	Herlev Hospital	Herlev

Sponsors (3)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	Herlev Hospital, Technical University of Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of time with glucose values < 3.9 mmol/l as measured by the continuous glucose monitor	Percentage	26 hours during closed-loop control
Secondary	Number of carbohydrate interventions to treat hypoglycemia		26 hours during closed-loop control
Secondary	Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by continuous glucose monitor and plasma glucose	Percentage	26 hours during closed-loop control
Secondary	Percentage of time with glucose values < 3.9 mmol/l as measured by plasma glucose	Percentage	26 hours during closed-loop control
Secondary	Percentage of time with glucose values in the range > 13.9 mmol/l measured by continuous glucose monitor and plasma glucose	Percentage	26 hours during closed-loop control
Secondary	Percentage of time with glucose values < 3.0 mmol/l as measured by continuous glucose monitor and plasma glucose	Percentage	26 hours during closed-loop control
Secondary	Mean blood glucose value measured by continuous glucose monitor and plasma glucose	mmol/L	26 hours during closed-loop control
Secondary	Number of hypoglycemic episodes < 3.9 mmol/l on continuous glucose monitor and plasma glucose	No.	26 hours during closed-loop control
Secondary	Continuous glucose monitored glycemic variability measured as SD	mmol/L	26 hours during closed-loop control
Secondary	Continuous glucose monitored glycemic variability measured as CV	percentage	26 hours during closed-loop control
Secondary	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	percentage	26 hours during closed-loop control
Secondary	Total insulin dose	units	26 hours during closed-loop control
Secondary	Total glucagon dose	mg	26 hours during closed-loop control
Secondary	Number of manual insulin boluses	No.	26 hours during closed-loop control
Secondary	Number of adverse events - Nausea	No of event if visual analog scale (0-100) increase >10 from baseline	26 hours during closed-loop control
Secondary	Number of adverse events - Headache	No of event if visual analog scale (0-100) increase >10 from baseline	26 hours during closed-loop control
Secondary	Number of adverse events - Palpitation	No of event if visual analog scale (0-100) increase >10 from baseline	26 hours during closed-loop control
Secondary	Number of vomits	No of event if visual analog scale (0-100) increase >10 from baseline	26 hours during closed-loop control
Secondary	Difference between actual and participant-estimated carbohydrate content in meals	g per meal	26 hours of closed-loop glucose control
Secondary	Mean Borg scale	Scale of perceived exertion from 6 (no effort activity) to 20 (max effort activity)	During 45 minutes exercise
Secondary	Physical activity intensity measured by ActiGraph GT9X Link	Percentage of sedentary activity	26 hours
Secondary	Sleep efficiency measured by ActiGraph GT9X Link	The ratio of total sleep time to time in bed	26 hours